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CN109589408B - Rice-shaped liquid metal nano particle and synthetic method and application thereof - Google Patents

Rice-shaped liquid metal nano particle and synthetic method and application thereof Download PDF

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CN109589408B
CN109589408B CN201811478965.6A CN201811478965A CN109589408B CN 109589408 B CN109589408 B CN 109589408B CN 201811478965 A CN201811478965 A CN 201811478965A CN 109589408 B CN109589408 B CN 109589408B
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gallium
melanin
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严骏杰
杨敏
王辛宇
潘栋辉
徐宇平
杨润琳
王立振
赵富宽
张波
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Jiangsu Institute of Nuclear Medicine
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Abstract

The invention discloses a synthesis method of a rice-shaped liquid metal nanoparticle, wherein the liquid metal is a gallium-indium eutectic crystal, the gallium-indium eutectic crystal is stabilized by using a melanin nanoparticle in the synthesis method, and the rice-shaped liquid metal nanoparticle is obtained by controlling the ultrasonic time to be more than or equal to 15min and the concentration of the melanin nanoparticle to be less than or equal to 0.25 mg/mL. The rice-shaped liquid metal nano particles have high photo-thermal conversion efficiency and high photo-thermal stability, and are a better photo-thermal treatment material. The invention discloses a rice-shaped liquid metal nanoparticle, wherein the liquid metal nanoparticle is a gallium-indium eutectic nanoparticle, the surface of the gallium-indium eutectic nanoparticle is chelated with a melanin nanoparticle, and the aspect ratio of the liquid metal nanoparticle is 2:1-3: 1. the rice-shaped liquid metal nanoparticles have high photothermal conversion efficiency, good photothermal stability, high biocompatibility and good tumor ablation effect, and can be used as photothermal treatment materials for tumor photothermal treatment.

Description

Rice-shaped liquid metal nano particle and synthetic method and application thereof
Technical Field
The invention relates to the technical field of liquid metal, in particular to a rice-shaped liquid metal nano particle and a synthetic method and application thereof.
Background
The nano material has special properties such as small-size effect, surface effect, quantum size effect, macroscopic quantum tunneling effect and the like, and thus has received wide attention. The performance of the nano-particles is closely related to the composition and the appearance of the nano-particles, and the metal nano-particles or the alloy nano-particles with specific shapes have wide application prospects in the fields of new energy, photoelectric information storage, catalytic chemistry, imaging, sensing, biomedicine and the like due to the special optical, electric, thermal, mechanical, magnetic and catalytic performances of the nano-particles.
The preparation method of the metal or alloy nano-particles mainly comprises two types: top-down (top-down) and bottom-up (bottom-up). The top-down method mainly adopts a physical method to disperse metal or alloy materials into nano-scale small particles, such as mechanical grinding, calcination, stretching, photoetching, microfluidic technology and the like. The bottom-up method generally adopts a chemical reduction method to reduce ions or complexes of metal or alloy into metal or alloy atoms, and the atoms are gathered into nano particles; depending on the reduction method, the method can be classified into a chemical reduction method, a light-induced reduction method, an electrodeposition method, and the like. In the process of preparing metal or alloy nanoparticles by the above method, particles having various shapes, sizes and size distributions can be obtained by controlling the growth of the nanomaterial.
As a special form of metal, liquid metal combines the softness and fluidity of liquid and the excellent conductive properties of metal, and is applied to wearable electronic devices, reconfigurable circuits, functional microfluidic devices, and the like. Among them, gallium-based liquid metals have been widely studied due to their low toxicity, low viscosity, and tunable melting point (at or below room temperature). Compared with the traditional large amount of liquid metal, the micron and nano liquid metal particles further expand the application of the micron and nano liquid metal particles in the fields of chemical catalysis, nano/micron electronic devices, biomedicine, energy and the like. However, due to the influence of the low melting point, good fluidity and easy aggregation of the liquid metal, the morphology of the liquid metal nanoparticles is difficult to control during the synthesis process, and it is difficult to obtain liquid metal nanoparticles with a specific shape.
Disclosure of Invention
Therefore, the technical problem to be solved by the present invention is to overcome the defect of difficult shape control of the liquid metal nanoparticles in the prior art, thereby providing a method for preparing the liquid metal nanoparticles in a rice shape.
Therefore, the invention provides the following technical scheme:
in a first aspect, the invention provides a method for synthesizing a rice-shaped liquid metal nanoparticle, wherein the liquid metal is a gallium-indium eutectic crystal, and the method comprises the following steps:
preparing a mixed solution containing melanin nanoparticles and gallium-indium eutectic, wherein the concentration of the melanin nanoparticles in the mixed solution is less than or equal to 0.25mg/mL;
and carrying out ultrasonic treatment on the mixed solution for more than or equal to 15min to obtain the rice-shaped liquid metal nanoparticles.
Preferably, in the above synthesis method, the concentration of the melanin nanoparticles in the mixed solution is 0.25 mg/mL.
Preferably, in the above synthesis method, the ultrasonic treatment further comprises: the temperature of the mixed solution is controlled to be less than or equal to 60 ℃.
Preferably, in the above synthesis method, the step of preparing the mixed solution containing the melanin nanoparticles and the gallium-indium eutectic includes: adding the melanin nanoparticles and the gallium-indium eutectic into a solvent, and introducing inert gas into the solvent to obtain a mixed solution containing the melanin nanoparticles and the gallium-indium eutectic; preferably, the solvent is water and the inert gas is argon.
Preferably, in the above synthesis method, the diameter of the melanin nanoparticles is 2-4 nm.
Preferably, in the above synthesis method, the preparation step of the melanin nanoparticles comprises:
carrying out acid-base treatment on the melanin granules to reduce the particle size of the melanin granules to a nanometer level so as to obtain a melanin nanoparticle solution;
and carrying out ultrafiltration, washing and drying treatment on the melanin nanoparticle solution to obtain the melanin nanoparticles.
Further preferably, in the above synthesis method, the acid-base treatment includes: adding melanin particles into a sodium hydroxide solution to obtain a melanin solution, and adjusting the pH of the melanin solution to 7 by using a hydrochloric acid solution to obtain a melanin nanoparticle solution;
the ultrafiltration treatment has a molecular weight cut-off of 30 kDa.
Preferably, the above synthesis method further comprises:
carrying out ultrasonic treatment on the mixed solution, removing the precipitate, and taking the upper layer slurry; centrifuging the slurry, and removing precipitates to obtain a solution dispersed with rice-shaped liquid metal nanoparticles; preferably, the centrifugation conditions are 1000rpm and the centrifugation time is 5 min.
In a second aspect, the invention provides a rice-shaped liquid metal nanoparticle, wherein the liquid metal nanoparticle is a gallium-indium eutectic nanoparticle, and the surface of the gallium-indium eutectic nanoparticle is chelated with a melanin nanoparticle; the aspect ratio of the liquid metal nanoparticles is 2:1-3: 1; preferably, the liquid metal nanoparticles have an aspect ratio of 2.3.
Preferably, the liquid metal nanoparticles in a rice form as described above, synthesized by the method of any one of claims 1 to 8.
In a third aspect, the present invention provides the use of the above-mentioned liquid metal nanoparticles in a rice form, or the liquid metal nanoparticles in a rice form synthesized by the above-mentioned method, as a photothermal therapy material.
In a fourth aspect, the present invention provides an application of the liquid metal nanoparticles in a rice form or synthesized by the above method in preparing a reagent for treating tumor.
In a fifth aspect, the present invention provides a photothermal therapeutic agent comprising the liquid metal nanoparticles in a rice form described above, or the liquid metal nanoparticles in a rice form synthesized by the method described above.
In a sixth aspect, the present invention provides a kit for tumor therapy, the kit comprising the liquid metal nanoparticles in a rice form, the liquid metal nanoparticles in a rice form synthesized by the above method, or the photothermal therapeutic agent.
The technical scheme of the invention has the following advantages:
1. the synthesis method of the rice-shaped liquid metal nanoparticles uses the melanin nanoparticles to stabilize the gallium-indium eutectic crystal. The gallium-indium eutectic is processed into small nano particles through ultrasonic treatment, meanwhile, cavitation bubbles in the liquid are subjected to vibration growth and collapse closure under the ultrasonic action, and when the bubbles collapse, transient high temperature and high pressure are generated to induce the solution to be lifted and ionized and excited. The heat and active oxygen in the ultrasonic process induce the generation of mono-hydroxy gallium oxide (GaOOH) on the surface of the gallium-indium eutectic nano particles. The catechol group in the melanin nano particle is chelated with the hydroxyl gallium oxide layer on the surface of the gallium-indium eutectic nano particle in a polyvalent manner, so that the solubility and the stability of the gallium-indium eutectic nano particle in the solution are obviously improved. In addition, the gallium-indium eutectic nanoparticles are further assembled and grown along with the increase of the temperature of the solution in the ultrasonic process. According to the invention, researches show that in the process of preparing the rice-shaped liquid metal nanoparticles by using the melanin nanoparticles and gallium indium eutectic ultrasound, the appearance of the liquid metal nanoparticles has certain dependence on the concentration of the melanin nanoparticles and the ultrasound time: when the ultrasonic time is less than 15min and the concentration of the melanin nano particles is more than 0.25mg/mL, only spherical liquid metal nano particles can be obtained, and the rice-shaped liquid metal nano particles can be synthesized by controlling the concentration of the melanin nano particles in the solution to be less than or equal to 0.25mg/mL and the ultrasonic time to be more than or equal to 15 min. In addition, the morphology of the liquid metal nanoparticles is selective to the type of liquid metal and the type of ligand that stabilizes the liquid metal, and when the type of ligand is changed (e.g., from a melanin nanoparticle to hyaluronic acid, PDMAPS, etc.) or the type of liquid metal is changed (e.g., from a Ga-in eutectic to a Ga-in-Sn eutectic, Ga-Sn alloy, etc.), the morphology of the liquid metal nanoparticles is changed.
According to the method, the gallium-indium eutectic is stabilized by the melanin nanoparticles for the first time, and the liquid metal nanoparticles with specific morphology are obtained by regulating the concentration of the melanin nanoparticles and the ultrasonic treatment time. The morphology of the nanoparticles is closely related to the physical and chemical properties thereof, and determines the special properties of the nanoparticles. The rice-shaped liquid metal nano particles obtained by the preparation method provided by the invention have better light-heat conversion efficiency, and after being irradiated by near infrared light (NIR), absorbed light energy is converted into heat energy. The rice-shaped morphology of the liquid metal nanoparticles and the surface-chelated melanin nanoparticles are mutually matched, so that the photo-thermal conversion efficiency of the nanoparticles is improved. In the three nano-morphology liquid metal nanoparticles provided by the invention, after the rice-shaped liquid metal nanoparticles are irradiated by near-infrared laser (808nm), the temperature rise amplitude (32.2 ℃) within 10 minutes is obviously higher than that of rod-shaped gallium-indium eutectic nanoparticles (28.8 ℃) and spherical gallium-indium eutectic nanoparticles (23.7 ℃); meanwhile, the light-heat stability of the rice-shaped liquid metal nano particles is high, no obvious temperature interval change occurs in the heating-cooling circulation process, the suspension dispersed with the rice-shaped liquid metal nano particles keeps high dispersion in the heating-cooling circulation process, and no precipitate is generated in the suspension. The rice-shaped liquid metal nano particles have high light-heat conversion efficiency and high photo-thermal stability, and are suitable for photo-thermal treatment (PTT, Photothermaltherapy) of diseases such as tumors and the like as photo-thermal therapeutic agents.
2. According to the synthesis method of the rice-shaped liquid metal nanoparticles, when the concentration of the melanin nanoparticles in the mixed solution is more than 0.25mg/mL, only spherical liquid metal nanoparticles can be synthesized; when the concentration of the melanin nanoparticles is controlled to be 0.25mg/mL, not only the rice-shaped liquid metal nanoparticles can be obtained, but also the dispersion stability of the liquid metal nanoparticles in the solution is further improved, and no precipitate is formed in the solution. When the concentration of the melanin nanoparticles is 0.25mg/mL, the liquid metal nanoparticles having the best stability can be obtained, compared with the liquid metal nanoparticles obtained from the melanin nanoparticles having a concentration of less than 0.25 mg/mL.
3. The synthesis method of the rice-shaped liquid metal nanoparticles provided by the invention has the advantages that the ultrasonic temperature is controlled to be less than or equal to 60 ℃, the temperature environment of ultrasonic treatment is controlled, the formation of the rice-shaped liquid metal nanoparticles is facilitated, and the appearance of the liquid metal nanoparticles is prevented from being changed (for example, when the ultrasonic temperature is higher than 70 ℃, the appearance of the liquid metal nanoparticles is changed into a rod shape). In the ultrasonic process, the temperature in the ultrasonic process is controlled by ultrasonic treatment in an ice bath environment. The temperature of the solution is increased from 0 ℃ in the ultrasonic process, and is finally controlled below 60 ℃.
4. The invention provides a method for synthesizing a rice-shaped liquid metal nanoparticle, which comprises the steps of adding a melanin nanoparticle and a gallium-indium eutectic crystal into a solvent, and introducing inert gas into the solvent to obtain a mixed solution containing the melanin nanoparticle and the gallium-indium eutectic crystal. Inert gas is introduced to protect the liquid metal and prevent the liquid metal from forming an oxide layer before ultrasonic treatment, so that the liquid metal nanoparticles gradually generate monohydroxy gallium oxide (GaOOH) on the surface of the liquid metal nanoparticles through active oxygen generated in the ultrasonic treatment.
5. According to the synthesis method of the rice-shaped liquid metal nanoparticles, in the preparation process of the melanin nanoparticles, the functional groups on the surfaces of the melanin particles are unified after being treated by acid and alkali solutions by performing water-soluble treatment on the melanin particles; meanwhile, in the acid-base treatment process, the particle size of the melanin particles is obviously reduced to obtain a melanin nanoparticle solution with the particle size of a nanometer grade; and (3) after the melanin nanoparticle solution is subjected to ultrafiltration treatment, effectively removing residual NaCl in the melanin nanoparticles, and finally washing and drying to obtain the melanin nanoparticles. When the melanin particles are processed into a nanometer grade, the metal chelating capacity of the melanin particles is obviously enhanced, and the chelation of the melanin particles and the monohydroxy gallium oxide layer on the surface of the gallium-indium eutectic nanoparticle is facilitated.
6. The invention provides a rice-shaped liquid metal nanoparticle, wherein the liquid metal is a gallium-indium eutectic nanoparticle, and the surface of the gallium-indium eutectic nanoparticle is chelated with a melanin nanoparticle. The melanin nano particles are chelated with the mono-hydroxy gallium oxide layer on the surface of the gallium-indium eutectic nano particles through the poly-valence chelating, so that the rice-shaped liquid metal nano particles stabilized by the melanin nano particles are obtained, and the aspect ratio of the liquid metal nano particles is 2:1-3: 1. the light-heat conversion efficiency (36.7%) of the meter-shaped liquid metal nano particles is high, is superior to rod-shaped gallium-indium eutectic nano particles (28.8%) and spherical gallium-indium eutectic nano particles (33.3%), and can effectively absorb near infrared light and convert the near infrared light into heat energy. The melanin nanoparticles are matched with the gallium-indium eutectic nanoparticles, so that the photo-thermal conversion efficiency and photo-thermal stability are high, the dispersion stability of the rice-shaped liquid metal nanoparticles in a solution is high, and the dispersion can be kept for a long time without generating precipitation.
7. The rice-shaped liquid metal nanoparticles provided by the invention or the rice-shaped liquid metal nanoparticles obtained by the synthesis method provided by the invention have high photo-thermal conversion efficiency and photo-thermal stability, and meanwhile, the rice-shaped liquid metal nanoparticles have good dispersion stability, low cytotoxicity and high biocompatibility, are good photo-thermal treatment materials, and can be effectively applied to photo-thermal treatment.
8. When the rice-shaped liquid metal nanoparticles provided by the invention or the liquid metal nanoparticles obtained by the synthesis method provided by the invention are applied to preparation of a reagent for treating tumors, the rice-shaped liquid metal nanoparticles can release heat after being excited by near-red light, so that the rice-shaped liquid metal nanoparticles can effectively ablate tumor tissues, and meanwhile, obvious weight loss is not caused, and the rice-shaped liquid metal nanoparticles have good biocompatibility. The rice-shaped liquid metal nanoparticles have high photothermal conversion efficiency and biocompatibility, so that the prepared reagent has a good treatment effect on tumors, and is suitable for preparing a tumor treatment reagent for clinical treatment of tumors.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a diagram of a process for synthesizing liquid metal nanoparticles in a rice form according to an embodiment of the present invention;
FIG. 2 is a High Resolution Transmission Electron Microscopy (HRTEM) image of a melanin nanoparticle of one embodiment of the present invention;
FIG. 3 is a graph of the results of characterizing the morphology and structure of a liquid metal nanoparticle in the form of a rice in accordance with one embodiment of the present invention;
FIG. 4 is a Scanning Transmission Electron Microscope (STEM) and energy dispersive X-ray Spectroscopy (EDS) of a liquid metal nanoparticle in the form of a meter in accordance with one embodiment of the present invention;
FIG. 5 is an X-ray diffraction pattern (XRD) of a nano-meter-shaped liquid metal particle in accordance with an embodiment of the present invention;
FIG. 6 is an FTIR spectrum of liquid metal nanoparticles in the form of a rice in accordance with one embodiment of the present invention;
FIG. 7 is an XPS spectrum of a rice-shaped liquid metal nanoparticle according to one embodiment of the present invention;
FIG. 8 is a solar chart of a rice-shaped liquid metal suspension according to one embodiment of the present invention;
FIG. 9 is a Transmission Electron Microscope (TEM) image of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 10 is a Transmission Electron Microscope (TEM) image of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 11 is a graph showing the results of Dynamic Light Scattering (DLS) detection of liquid metal nanoparticles according to an example of the present invention;
FIG. 12 is a zeta potential diagram of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 13 is a graph of ultraviolet-visible absorption spectra (UV-vis) of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 14 is a Transmission Electron Microscope (TEM) image of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 15 is a solar image of a liquid metal nanoparticle suspension according to an experimental example of the present invention;
FIG. 16 is a graph showing the Dynamic Light Scattering (DLS) detection result of liquid metal nanoparticles according to an example of the present invention
FIG. 17 is a zeta potential diagram of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 18 is a Transmission Electron Microscope (TEM) image of gallium indium eutectic nanoparticles stabilized with different ligands according to an experimental example of the present invention;
FIG. 19 is a graph of the stability results of gallium indium eutectic nanoparticles stabilized with different ligands according to an experimental example of the present invention;
FIG. 20 is a Transmission Electron Microscope (TEM) image of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 21 is a Transmission Electron Microscope (TEM) image of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 22 is a Transmission Electron Microscope (TEM) image of liquid metal nanoparticles according to an experimental example of the present invention;
FIG. 23 is an ultraviolet-visible absorption spectrum of liquid metal nanoparticles of different morphologies according to an experimental example of the present invention;
FIG. 24 is a graph showing photothermal response curves of liquid metal nanoparticles of different morphologies in accordance with an experimental example of the present invention;
FIG. 25 is a photo-thermal response curve of near-infrared laser irradiation of the in-gallium eutectic nanoparticle in an off-meter shape at different frequencies according to an example of the present disclosure;
FIG. 26 is a photo-thermal response curve of different concentrations of the in-gallium eutectic nanoparticle suspensions of the present invention;
FIG. 27 is a graph showing a cyclic photothermal response of a Mimi-shaped GaIn eutectic nanoparticle according to an example of the present invention;
FIG. 28 is a linear plot of temperature cooling time-Ln (Δ T/Δ Tmax) fit for liquid metal nanoparticles of different morphologies according to an experimental example of the present invention;
FIG. 29 is a graph showing the results of cytotoxicity assays (MTT) of indium gallium eutectic nanoparticles in a shape of a meter with and without irradiation of laser light in accordance with an example of the present invention;
FIG. 30 is a Calcein AM/PI staining pattern of 4T1 cells according to an example of the present invention;
FIG. 31 is a dynamic TEM image of Mimi-shaped GaIn eutectic nanoparticles under continuous laser irradiation in accordance with an example of the present invention;
FIG. 32 is an infrared thermal image of a mouse under laser illumination at various times in accordance with an experimental example of the present invention;
FIG. 33 is a bioluminescence map of 4T1 tumor growth in mice treated with PBS, PBS and laser irradiation, and the gallium indium diselenide eutectic nanoparticles and laser irradiation, respectively, in accordance with an experimental example of the present invention;
FIG. 34 is a graph of immunohistochemical staining of 4T1 tumor tissue in mice treated with gallium indium gallium nitride eutectic nanoparticles and laser irradiation, gallium indium gallium nitride eutectic nanoparticles treatment, PBS and scaffolding irradiation, and laser irradiation according to an experimental example of the present invention;
FIG. 35 is a graph showing the results of the tumor growth and survival status tests of mice from different treatment groups according to an example of the present invention.
Detailed Description
The technical solutions of the present invention will be described clearly and completely below, and it should be apparent that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. In addition, the technical features involved in the different embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The apparatus involved in the following examples is as follows:
nuclear magnetic resonance apparatus Varian Mercury 400; a scanning electron microscope FEI Verios 460L; cryo-scanning electron microscope JEOL7600F; transmission electron microscopy JEOL 2000FX, FEI Titan 80-300; an X-ray diffractometer Rigaku SmartLab; dynamic light scattering Malvern Zetasizer Nano ZS; laser confocal microscope Carl Zeiss LSM 710; ultrasonic FisherbrandTM Model 505。
The experimental reagents used in the following examples are as follows:
gallium-indium eutectic, gallium-indium-tin eutectic and gallium-tin alloy are purchased from AlfaAesar; hyaluronic acid purchased from fredabiochem. Other reagents were purchased from Sigma.
The 4T1 cells used for cytotoxicity assays in the following experimental examples were derived from the American ATCC cell bank.
Example 1
The present embodiment provides a method for synthesizing liquid metal nanoparticles in a rice shape, wherein the liquid metal is gallium-indium eutectic (also called gallium-indium alloy). The synthesis process of the rice-shaped liquid metal nanoparticles is shown in fig. 1, and the specific steps are as follows:
1. synthesis of water-soluble melanin nanoparticles
Under vigorous stirring, 50mg of melanin granules were dissolved in 20mL of 0.1N NaOH to obtain a melanin solution, and 0.1N HCl was added dropwise to the alkaline solution while applying ultrasound to neutralize the solution to pH 7, thereby obtaining a melanin nanoparticle solution. In the acid-base treatment process, the surface functional groups of the melanin granules are unified, and the melanin granules are changed into easily soluble nano-scale particles from particles with large particle size and low water solubility.
Use of
Figure BDA0001891935650000061
The ultrafiltration tube is used for purifying the melanin nano particle solution, and the intercepted relative molecular mass of the ultrafiltration tube is 30 kDa. Washing the purified solution with deionized water to remove sodium chloride, and then freeze-drying to obtain melanin nanoparticle powder, yield: 65.4 percent.
The chemical structure of the melanin nanoparticles is shown below:
Figure BDA0001891935650000071
2. synthesis of rice-shaped liquid metal nanoparticles
Adding 3.0mg of melanin nanoparticles and 80 mu L of gallium-indium eutectic into 12mL of deionized water, and introducing argon into the water for 10 minutes to obtain a mixed solution containing the melanin nanoparticles and the gallium-indium eutectic.
And (3) carrying out ultrasonic treatment on the mixed solution in an ice bath environment, wherein the ultrasonic treatment time is 15 min. The ultrasonic instrument parameters were as follows: frequency, 20 kHz; rated power, 500 watts; the diameter of the probe is 3 mm; the amplitude is 35%.
After ultrasonic treatment, discarding large-particle precipitates, and taking upper-layer slurry; and centrifuging the upper layer slurry at the rotating speed of 1000rpm for 5min, further removing large-particle precipitates, purifying the solution, and obtaining suspension in which the rice-shaped liquid metal nanoparticles are uniformly dispersed, namely the rice-shaped gallium-indium eutectic nanoparticle suspension.
The morphology and structure of the melanin nanoparticles are characterized as follows:
the morphology of the melanin nanoparticles was observed using a High Resolution Transmission Electron Microscope (HRTEM). As shown in fig. 2a and 2b, fig. 2a is a high resolution transmission electron microscope image of the melanin nanoparticles with a scale of 10nm, and it can be seen from fig. 2 that the melanin nanoparticles have good dispersibility, small particle size and approach to spherical shape. The results shown in fig. 2b were obtained by counting the diameters of the melanin nanoparticles in the HRTEM images, and it can be seen from fig. 2b that the melanin nanoparticles have relatively concentrated particle diameter distribution, and the average particle diameter is 3.1 ± 0.6 nm.
The rice-shaped liquid metal nanoparticles are characterized as follows:
1. morphology and structural characterization
FIG. 3 is a graph of the characterization results of the morphology and structure of the liquid metal nanoparticles in a rice shape. Wherein, fig. 3b shows a Transmission Electron Microscope (TEM) image of the liquid metal nanoparticles in a rice form, ruler, 200 nm. As can be seen from fig. 3b, the liquid metal nanoparticles are in a meter shape, and the aspect ratio of the liquid metal nanoparticles is counted to obtain that the aspect ratio of the liquid metal nanoparticles is between 2:1-3:1, the average value of the aspect ratio thereof is 2.3. FIG. 3c shows a High Resolution Transmission Electron Microscope (HRTEM) image, scale, 50nm of a liquid metal nanoparticle in the form of a rice; fig. 3d shows dark field Scanning Transmission Electron Microscope (STEM) images, scale, 50nm of the liquid metal nanoparticles in a rice form. As can be seen from fig. 3c and 3d, the liquid metal nanoparticles in a rice shape are assembled from small nanoparticles. Fig. 3e shows a Scanning Electron Microscope (SEM) image of the liquid metal nanoparticles in a beige form, scale, 500 nm; FIG. 3f shows a Cryo-scanning electron microscope (Cryo-SEM) image of liquid metal nanoparticles in the form of a rice, ruler, 250 nm. As can be seen from fig. 3e and 3f, the liquid metal nanoparticles in a rice shape are assembled from small nanoparticles. Fig. 3e and 3f show the morphology of the liquid metal nanoparticles in a rice form in a dry state and a liquid state dispersed in a solution, and it can be seen from fig. 3e and 3f that the dry or liquid state of the liquid metal nanoparticles in a rice form does not affect the morphology of the nanoparticles.
2. Structural and elemental analysis
The structure and elemental composition of the liquid metal nanoparticles in the form of a rice were analyzed using scanning transmission electron microscopy and energy dispersive X-ray spectroscopy (STEM-EDS). The results are shown in FIG. 4: figure 4g shows a high angle annular dark field image of a scanning transmission electron microscope, scale, 200 nm. Fig. 4 h-4 j show element distribution diagrams of the rice-shaped liquid metal nanoparticles observed by STEM-EDS, fig. 4K is a fusion diagram of fig. 4 h-4 j, and as can be seen from fig. 4 h-4K, the rice-shaped liquid metal nanoparticles are distributed with not only Ga element and In element In the gallium-indium eutectic, but also oxygen element uniformly.
FIG. 5 is an X-ray diffraction diagram of a liquid metal nanoparticle in a form of a meter, wherein EGaInnanorice represents a liquid metal nanoparticle in a form of a meter (i.e., a gallium-indium eutectic nanoparticle in a form of a meter). As can be seen from fig. 5, the In and GaOOH contained In the liquid metal nanoparticles In a rice form were consistent with the observation results of STEM-EDS.
3. Surface radical, elemental analysis
Characterization of surface groups of the liquid metal nanoparticles in the form of a meter by Fourier transform Infrared Spectroscopy (FTIR), FIG. 6 shows FTIR spectra of liquid metal nanoparticles in the form of a meter, FIG. 6EGaInnanorice represents a rice-shaped liquid metal nanoparticle (namely, a rice-shaped gallium-indium eutectic nanoparticle), and MNPs represent melanin nanoparticles. As can be seen from FIG. 6, the Fourier transform infrared spectrum of the liquid metal nanoparticles in a form of rice is 1370cm-1，1593cm-1，1716cm-1And 3370cm-1Several main bands as the center, 1593 cm-1And 3370cm-1The bands at (a) are due to stretching vibrations of C ═ C and OH bonds, respectively. 1716cm-1The signal at (a) is assigned to C ═ O, indicating the presence of a quinone. 1716cm after the melanin nano particles and the gallium-indium eutectic interaction form the meter-shaped gallium-indium eutectic nano particles-1The absorption at (A) is significantly reduced; at the same time, at 1023cm-1And 1261cm-1Two new absorption peaks appear, which are the bending vibration band of Ga-OH and the stretching vibration band of C-OH from carboxyl or phenol, respectively. These data indicate that the quinone intermediate of the melanin nanoparticles may be converted to catechol and coordinated to the gallium oxyhydroxide (GaOOH) on the surface of the gallium indium eutectic.
The surface elements of the liquid metal nanoparticles in a rice form were further analyzed using X-ray photoelectron spectroscopy (XPS), which is shown in fig. 7. Fig. 7a shows a full spectrum of the X-ray photoelectron spectrum, and as can be seen from fig. 7a, the surface of the rice-shaped liquid metal nanoparticles mainly contains C, O, N and Ga elements. FIG. 7b shows a high resolution C1s spectrum fitted with C1s, and FIG. 7b reveals four different types of carbon: CH (CH)x，C-NH2(ii) a C-O, C-N; c ═ O and pi → pi. Fig. 7C shows a high resolution O1s spectrum fitted with O1s, 531.6eV in fig. 7C corresponding to the formation of metal oxide (O-Ga), and the O-C signal peak at 530.3eV is much stronger than the O ═ C signal peak at 534.5 eV. FIG. 7c shows a high resolution Ga 3d spectrum fitted with Ga 3d, and FIG. 7c demonstrates Ga and Ga3+Is present. From the XPS spectrum of the rice-shaped liquid metal nanoparticles of fig. 7, it can be seen that: the melanin nano particles are sequestered by catechol and mono-hydroxy gallium oxide GaOOH on the surfaces of the gallium-indium eutectic nano particles, so that the melanin nano particles are successfully bonded on the surfaces of the gallium-indium eutectic nano particles.
The bonding strength of the melanin nanoparticles and the gallium-indium eutectic is detected by observing a heliogram (figure 8) of a freshly prepared rice-shaped liquid metal nanoparticle suspension and a rice-shaped liquid metal suspension subjected to gravity-induced precipitation, wherein MNPs in figure 8 represent the melanin nanoparticle suspension, and Nanorice represents the rice-shaped liquid metal nanoparticle suspension. From the detection results in fig. 8, after the precipitation of the liquid metal nanoparticles in a rice shape is induced by gravity, the color of the melanin nanoparticles is not observed in the supernatant, which indicates that the melanin nanoparticles and the gallium-indium eutectic crystal have strong interaction.
Deducing the forming process of the rice-shaped liquid metal nano particles from the characterization result of the rice-shaped liquid metal nano ions: the gallium-indium eutectic is processed into small nano particles through strong shearing force by ultrasound, transient high-temperature and high-pressure environment is generated by cavitation bubbles in the liquid state, and monohydroxy gallium oxide (GaOOH) is generated on the surfaces of the gallium-indium eutectic nano particles by heat and active oxygen generated in the ultrasound process. The o-catechol group in the melanin nano particle is chelated with the monohydroxy gallium oxide layer on the surface of the gallium-indium eutectic nano particle in a polyvalent manner, so that the gallium-indium eutectic nano particle with improved water solubility and dispersion stability is obtained. Meanwhile, along with the further increase of the temperature in the ultrasonic process, the gallium-indium eutectic nanoparticles are further assembled and grown to finally obtain the rice-shaped liquid metal nanoparticles (namely, the rice-shaped gallium-indium eutectic nanoparticles).
Comparative example 1
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 2 min.
Comparative example 2
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 4 min.
Comparative example 3
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 6 min.
Comparative example 4
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 8 min.
Comparative example 5
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 10 min.
Comparative example 6
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 20 min.
Comparative example 7
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 30 min.
Comparative example 8
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) carrying out ultrasonic treatment on the mixed solution in the step 2 for 40 min.
Comparative example 9
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: in step 2, 0.6mg of melanin nanoparticles and 80 μ L of gallium-indium eutectic are added to 12mL of deionized water.
Comparative example 10
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: in step 2, 1.2mg of melanin nanoparticles and 80 μ L of gallium-indium eutectic are added to 12mL of deionized water.
Comparative example 11
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: in step 2, 1.8mg of melanin nanoparticles and 80 μ L of gallium-indium eutectic are added to 12mL of deionized water.
Comparative example 12
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: in step 2, 4.8mg of melanin nanoparticles and 80 μ L of gallium-indium eutectic are added to 12mL of deionized water.
Comparative example 13
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: in step 2, 7.2mg of melanin nanoparticles and 80 μ L of gallium-indium eutectic are added to 12mL of deionized water.
Comparative example 14
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: in step 2, 9.0mg of melanin nanoparticles and 80 μ L of gallium-indium eutectic are added to 12mL of deionized water.
Comparative example 15
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-indium-tin eutectic.
Comparative example 16
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 2 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-indium-tin eutectic.
Comparative example 17
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 3 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-indium-tin eutectic.
Comparative example 18
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 4 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-indium-tin eutectic.
Comparative example 19
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 5 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-indium-tin eutectic.
Comparative example 20
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 6 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-indium-tin eutectic.
Comparative example 21
This comparative example provides a method of synthesizing liquid metal nanoparticles, which differs from the synthesis method provided in example 1 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-tin eutectic.
Comparative example 22
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 2 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-tin eutectic.
Comparative example 23
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 3 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-tin eutectic.
Comparative example 24
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 4 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-tin eutectic.
Comparative example 25
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 5 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-tin eutectic.
Comparative example 26
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method provided in comparative example 6 only in that: and (3) replacing the gallium-indium eutectic in the step (2) with a gallium-tin eutectic.
Comparative example 27
The comparative example provides a method for synthesizing liquid metal nanoparticles, which comprises the following specific steps:
1. synthesis of methacrylated Hyaluronic Acid (HA)
2.0g of hyaluronic acid was dissolved in 50mL of deionized water at 4 ℃, and then 1.6mL of methacrylic anhydride was added dropwise to the solution to obtain a reaction mixture. The pH of the reaction mixture was adjusted to 8-9 by adding 1N NaOH and stirred at 4 ℃ for 30 hours to obtain a double bond-modified polymer.
The resulting polymer was dialyzed against deionized water for 3 days for purification treatment, and then lyophilized to obtain methacrylated hyaluronic acid, yield: 84.7 percent.
The structure of methacrylated hyaluronic acid is shown below:
Figure BDA0001891935650000121
2. synthesis of liquid metal nanoparticles
5.0mg of methacrylated hyaluronic acid and 80 mu L of gallium-indium eutectic are added into 12mL of deionized water, and argon is introduced into the water for 10 minutes to obtain a mixed solution containing the methacrylated hyaluronic acid and the gallium-indium eutectic.
And (3) carrying out ultrasonic treatment on the mixed solution in an ice bath environment, wherein the ultrasonic treatment time is 15 min. The ultrasonic instrument parameters were as follows: frequency, 20 kHz; rated power, 500 watts; the diameter of the probe is 3 mm; the amplitude is 35%.
After ultrasonic treatment, discarding large-particle precipitates, and taking upper-layer slurry; and centrifuging the upper layer slurry at the rotating speed of 1000rpm for 5min, further removing large-particle precipitates, and purifying the solution to obtain the liquid metal nanoparticles with stable methacrylic acid Hyaluronic Acid (HA).
Comparative example 28
The comparative example provides a method for synthesizing liquid metal nanoparticles, which comprises the following specific steps:
1. synthesis of Poly [ 2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (PDMAPS)
DMAPS (279.4mg, 1.0mmol), PEG950(850mg, 0.895mmol), 4-cyano-4- (thiobenzoyl) pentanoic acid (18.6mg, 0.067mmol) and 4, 4' -azobis (4-cyanopentanoic acid) (4.7mg, 0.0168mmol) were dissolved in 0.5M sodium chloride solution to adjust the pH of the solution to 7. Oxygen was then removed by three freeze-evacuate-thaw cycles.
And (3) reacting the deoxidized mixture in an oil bath preheated at 70 ℃ for 20 hours, and then dialyzing in deionized water for 3 days for purification treatment to obtain light pink spongy powder, namely PDMAPS. Yield: 87.6 percent.
The chemical structure of PDMAPS is shown below:
Figure BDA0001891935650000131
2. synthesis of liquid metal nanoparticles
Adding 5.0mg of PDMAPS and 80 mu L of gallium-indium eutectic into 12mL of deionized water, and introducing argon into the water for 10 minutes to obtain a mixed solution containing the PDMAPS and the gallium-indium eutectic.
And (3) carrying out ultrasonic treatment on the mixed solution in an ice bath environment, wherein the ultrasonic treatment time is 15 min. The ultrasonic instrument parameters were as follows: frequency, 20 kHz; rated power, 500 watts; the diameter of the probe is 3 mm; the amplitude is 35%.
After ultrasonic treatment, discarding large-particle precipitates, and taking upper-layer slurry; and centrifuging the upper layer slurry at the rotating speed of 1000rpm for 5min, further removing large-particle precipitates, and purifying the solution to obtain the PDMAPS stable liquid metal nanoparticles.
Comparative example 29
The comparative example provides a method for synthesizing liquid metal nanoparticles, which comprises the following specific steps:
5.0mg of Polyetherimide (PEI) and 80. mu.L of gallium indium eutectic were added to 12mL of deionized water, and argon gas was introduced into the water for 10 minutes to obtain a mixed solution containing the polyetherimide and the gallium indium eutectic.
And (3) carrying out ultrasonic treatment on the mixed solution in an ice bath environment, wherein the ultrasonic treatment time is 15 min. The ultrasonic instrument parameters were as follows: frequency, 20 kHz; rated power, 500 watts; the diameter of the probe is 3 mm; the amplitude is 35%.
After ultrasonic treatment, discarding large-particle precipitates, and taking upper-layer slurry; and centrifuging the upper layer slurry at the rotating speed of 1000rpm to further remove large-particle precipitates so as to purify the solution, wherein the PEI stabilizes the liquid metal nanoparticles. Wherein the chemical structure of PEI is as follows:
Figure BDA0001891935650000132
comparative example 30
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method for synthesizing provided in comparative example 27 only in that: in step 2, 4.8mg of methacrylated Hyaluronic Acid (HA) and 80. mu.L of gallium indium co-crystal were added to 12mL of deionized water.
Comparative example 31
This comparative example provides a method for synthesizing liquid metal nanoparticles, which is different from the method for synthesizing provided in comparative example 27 only in that: in step 2, 7.2mg of methacrylated Hyaluronic Acid (HA) and 80. mu.L of gallium indium co-crystal were added to 12mL of deionized water.
Experimental example 1
In this experimental example, the liquid metal nanoparticles in example 1 and comparative examples 1 to 8 were characterized by ultraviolet-visible absorption spectroscopy, Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), and zeta potential to monitor the kinetic process of liquid metal nanoparticle formation at different ultrasound times. The monitoring results were as follows:
FIG. 9 shows Transmission Electron Microscope (TEM) images, scale, 100nm of liquid metal nanoparticles in example 1 and comparative examples 1-6; fig. 10 shows Transmission Electron Microscope (TEM) images of the liquid metal nanoparticles in comparative examples 7 to 8. As can be seen from fig. 9 and 10, when the time of the ultrasonic treatment is less than 15min, the liquid metal nanoparticles are spherical, and when the ultrasonic time reaches 15min, the liquid metal nanoparticles grow to a rice shape. Further prolonging the ultrasonic time can increase the temperature of the mixed solution, slightly aggregate the rice-shaped liquid metal nano particles, increase the particle size and still retain the rice-shaped morphology. When the ultrasonic time is prolonged to 30min and 40min, the temperature of the mixed solution is further increased, and when the particle size of the liquid metal nano particles is not obviously changed, the morphology of the rice-shaped liquid metal nano particles is well maintained.
Fig. 11 is a graph showing the results of Dynamic Light Scattering (DLS) detection of the liquid metal nanoparticles in example 1 and comparative examples 1 to 6, and it can be seen from fig. 11 that the size of the liquid metal nanoparticles did not significantly change at the sonication time of 2min to 10min, the liquid metal nanoparticles began to be deformed and fused after 10min, and at 15min, the liquid metal nanoparticles grew in a rice shape having a polydispersity index (PDI) of 0.083.
Fig. 12 shows a zeta potential diagram of the liquid metal nanoparticles in example 1 and comparative examples 1 to 6, and it can be seen from fig. 12 that the zeta potential of the liquid metal nanoparticles gradually decreases with the increase of the ultrasonic time, indicating that the hydroxyl and carboxyl groups of the melanin nanoparticles may participate in the bonding process with the gallium indium eutectic nanoparticles in addition to catechol.
Fig. 13 shows uv-vis absorption spectra of the liquid metal nanoparticles in example 1 and comparative examples 1 to 6, and it can be seen from fig. 13 that the absorption peak of the liquid metal nanoparticles at around 400nm is slowly increased and the color of the liquid metal nanoparticle suspension is gradually changed from dark gray to light gray as the ultrasonic time is prolonged.
Experimental example 2
In this experimental example, the liquid metal nanoparticles of example 1 and comparative examples 9 to 14 were characterized by a Transmission Electron Microscope (TEM), observation of a daylight image of a liquid metal nanoparticle suspension, Dynamic Light Scattering (DLS), and zeta potential to detect the concentration dependence of the liquid metal nanoparticles on melanin nanoparticles. The detection results are as follows:
fig. 14 shows Transmission Electron Microscope (TEM) images, scale, 250nm of the liquid metal nanoparticles of example 1 and comparative examples 12-14. As can be seen from fig. 14, when the concentration of the melanin nanoparticles is 0.25mg/mL, the liquid metal nanoparticles can be obtained in a rice shape, and when the melanin nanoparticles are fed at a higher concentration, the liquid metal nanoparticles grow into a spherical shape.
FIG. 15 shows solar images of the liquid metal nanoparticle suspensions of example 1 and comparative examples 9-14. As can be seen from fig. 15, when the concentration of the melanin nanoparticles is less than 0.25mg/mL, the stability of the liquid metal nanoparticles is affected, and precipitation occurs after the standing.
Fig. 16 and 17 show graphs of Dynamic Light Scattering (DLS) detection results and zeta potential graphs of the liquid metal nanoparticles in example 1 and comparative examples 12 to 14, respectively. As can be seen from fig. 16 and 17, the size of the liquid metal nanoparticles is reduced by the high-dosage melanin nanoparticles, and the increase of the zeta negative potential on the surface of the liquid metal nanoparticles indicates that after the concentration of the melanin nanoparticles is increased, more binding sites are provided for the gallium-indium eutectic nanoparticles, and the probability of fusion and assembly of the gallium-indium eutectic nanoparticles is reduced.
Experimental example 3
In the experimental example, the liquid metal nanoparticles in example 1 and comparative examples 27 to 31 are characterized by a Transmission Electron Microscope (TEM) to detect the morphology change of gallium-indium eutectic nanoparticles stabilized by different ligands. The detection results are as follows:
FIG. 18 shows Transmission Electron Microscope (TEM) images of different ligand-stabilized Ga-in eutectic nanoparticles, with the first horizontal column from left to right showing Melanin Nanoparticle (MNP) -stabilized Ga-in eutectic nanoparticles of example 1, and Polyetherimide (PEI) -stabilized Ga-in eutectic nanoparticles of comparative example 29; the second horizontal column in the figure shows, from left to right, the methacrylated Hyaluronic Acid (HA) -stabilized gallium-indium eutectic nanoparticles of comparative example 27, and the poly [ 2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (PDMAPS) -stabilized gallium-indium eutectic nanoparticles of comparative example 28. As can be seen from fig. 18, the positively charged PEI has good stability, and can disperse gallium indium eutectic nanoparticles into uniform nanospheres through electrostatic interaction. HA can also stabilize gallium indium eutectic particles by hydroxyl groups, resulting in nanospheres, but with a broad polydispersity index. When PDMAPS is used as a ligand, only irregular gallium-indium eutectic nanoparticles can be formed. FIG. 18 shows that polymers (e.g., PEI and HA) with reactive groups (amino, thiol, hydroxyl, etc.) can stabilize the gallium-indium eutectic nanoparticles, but the morphology of the gallium-indium eutectic nanoparticles can only be controlled to be spherical, and only the melanin nanoparticles are selected to stabilize the gallium-indium eutectic nanoparticles, so that the rice-shaped liquid metal nanoparticles with good dispersion stability can be obtained.
FIG. 19 shows the stability of gallium indium eutectic nanoparticles stabilized by different ligands, in which the polyethylene glycol-sulfhydryl (PEG-SH), PEI and melanin nanoparticles are used as ligands in sequence from left to right. As can be seen from fig. 19, the stability of the gallium-indium eutectic nanoparticle stabilized by the melanin nanoparticles is significantly higher than that of molecules containing thiol and having positive charges, which indicates that the stability of the liquid metal nanoparticle in a rice shape is good.
Fig. 20 shows Transmission Electron Microscope (TEM) images, scale, 200nm of the liquid metal nanoparticles in comparative example 27 and comparative examples 30-31. As can be seen from fig. 20, different from the liquid metal nanoparticles with stable melanin nanoparticles, Hyaluronic Acid (HA) with different concentrations HAs no significant effect on the morphology of the liquid metal nanoparticles, and the gallium-indium eutectic nanoparticles with stable HA remain as nanospheres as the HA concentration increases.
Experimental example 4
In this example, the liquid metal nanoparticles in comparative examples 15 to 26 were characterized by a Transmission Electron Microscope (TEM) to detect stable ga, in, sn nanoparticles of melanin nanoparticles and morphology changes of ga, sn nanoparticles at different ultrasonic times. The detection results are as follows:
fig. 21 shows Transmission Electron Microscope (TEM) images of the liquid metal nanoparticles in comparative examples 15 to 20, and fig. 22 shows Transmission Electron Microscope (TEM) images of the liquid metal nanoparticles in comparative examples 21 to 26. As can be seen from fig. 21 and 22, at different ultrasonic times (4min, 6min, 8min, 10min, 15min, and 20min), the morphology of the gallium indium tin eutectic nanoparticles stabilized by the melanin nanoparticles (fig. 21) and the morphology of the gallium tin eutectic nanoparticles stabilized by the melanin nanoparticles (fig. 22) can only exhibit a nanosphere shape.
Experimental example 5
In this experimental example, the photothermal properties of liquid metal nanoparticles (in-meter-shaped gallium-indium eutectic nanoparticles, spherical gallium-indium eutectic nanoparticles, and rod-shaped gallium-indium eutectic nanoparticles) having different morphologies and stabilized by melanin nanoparticles are measured, and the measurement method is as follows:
1. the light absorption properties of the meter-shaped gallium-indium eutectic nanoparticles, the rod-shaped gallium-indium eutectic nanoparticles and the spherical gallium-indium eutectic nanoparticles are characterized by ultraviolet-visible absorption spectrum.
2. The wavelength is 808nm, and the power is 2.0W cm-2The near-infrared laser irradiates liquid metal nanoparticle suspensions with different morphologies for 10min, water is used as a control, and a photo-thermal response curve of the liquid metal nanoparticles is drawn according to the temperature rise value of the suspensions in the irradiation process.
3. And drawing a photo-thermal response curve according to the temperature rise values of the nano-meter-shaped gallium-indium eutectic nanoparticles irradiated by the near-infrared laser with different powers.
4. And drawing a photo-thermal response curve according to the temperature rise values of the nano-meter-shaped gallium-indium eutectic nanoparticles with different concentrations irradiated by the near-infrared laser.
5. And drawing a circulating photo-thermal response curve of the meter-shaped liquid metal nano particles to detect the photo-thermal stability of the meter-shaped gallium-indium eutectic nano particles.
6. Calculating the photo-thermal conversion efficiency:
the photothermal conversion efficiency (η) was calculated by the Roper method.
Figure BDA0001891935650000161
Figure BDA0001891935650000162
Wherein Δ TmaxRepresents the temperature change of the sample at the maximum steady-state temperature; delta TmaxAnd s represents the solvent (e.g., H) at the maximum steady state temperature2O) temperature change; i is the NIR laser power, equal to the power density multiplied by the illuminated area; a is the absorbance of the sample at 808 nm; m issAnd CsMass and heat capacity of the solvent, respectively; τ is the sampling system time constant, ln (Δ T/Δ T) can be determined by linear curve fitting of the temperature cooling timemax)。
The detection results are as follows:
fig. 23 shows ultraviolet-visible absorption spectra of liquid metal nanoparticles of different morphologies, and it can be seen from fig. 23 that the light absorption of the in-meter-shaped gallium-indium eutectic nanoparticles is greater than that of the rod-shaped gallium-indium eutectic nanoparticles and that of the spherical gallium-indium eutectic nanoparticles. FIG. 24 shows the photo-thermal response curves of different morphologies of liquid metal nanoparticles, and it can be seen from FIG. 24 that the laser is near-infrared laser (power: 2.0W cm) at 808nm-2) The temperature of the liquid metal nanoparticle suspension with different morphologies (the concentration is 0.5mg/mL respectively) is increased by the maximum (32.2 ℃) within 10 minutes by irradiating the liquid metal nanoparticle suspension with different morphologies, while the temperature of the rod-shaped gallium-indium eutectic nanoparticle and the spherical gallium-indium eutectic nanoparticle suspension is increased by 28.8 ℃ and 23.7 ℃ respectively. In contrast, water exhibits only a slight temperature rise under the same experimental conditions (<At 2 ℃ C.). Compared with rod-shaped gallium-indium eutectic nanoparticles and spherical gallium-indium eutectic nanoparticles, the nanometer-shaped gallium-indium eutectic nanoparticles can effectively absorb near infrared light and convert the near infrared light into heat energy.
Fig. 25 shows a photo-thermal response curve of the nano-sized indium gallium eutectic nanoparticles irradiated by the near-infrared laser with different frequencies, and it can be seen from fig. 25 that the photo-thermal conversion effect of the nano-sized indium gallium eutectic nanoparticles is related to the laser frequency, and the temperature rise value of the nano-sized indium gallium eutectic nanoparticles increases with the increase of the laser frequency, thus showing the dependency on the laser frequency. Fig. 26 shows the photo-thermal response curves of the suspensions of the in-gallium eutectic nanoparticles with different concentrations, and it can be seen from fig. 26 that the photo-thermal conversion effect of the in-gallium eutectic nanoparticles is related to the suspension concentration, and as the concentration increases, the temperature rise value of the in-gallium eutectic nanoparticles increases, showing the dependency on the suspension concentration.
Fig. 27 shows the cyclic photothermal response curve of the in-gallium eutectic nanoparticle in the form of a meter, and the temperature change during 4 heating-cooling cycles is monitored in fig. 27. As can be seen from fig. 27, there is no significant change in the temperature range during the heating-cooling cycle, and the suspension of the indium gallium eutectic nanoparticles remains highly dispersed and no precipitate is generated during the heating-cooling cycle, which indicates that the indium gallium eutectic nanoparticles have high photo-thermal stability and can avoid melting and losing typical absorption peaks under repeated near-infrared laser irradiation.
FIG. 28 shows the temperature cooling time-Ln (Δ T/Δ T) of liquid metal nanoparticles of different morphologiesmax) Fitted linear curve. The photothermal conversion efficiency (η) of the meter-shaped gallium-indium eutectic nanoparticle suspension, the rod-shaped gallium-indium eutectic nanoparticle suspension and the spherical gallium-indium eutectic nanoparticle suspension was calculated by the method of Roper, and the results were 36.7%, 28.8% and 33.3%, respectively.
According to the detection results, after the nanometer gallium-indium eutectic nano particles are irradiated by near infrared light (NIR), the absorbed light energy is converted into heat energy, and the light-heat conversion efficiency is better. The melanin nano particles are subjected to polyvalent chelation on the surfaces of the gallium-indium eutectic nano particles, so that the obtained rice-shaped gallium-indium eutectic nano particles have higher photo-thermal conversion efficiency than rod-shaped and spherical gallium-indium eutectic nano particles, have higher photo-thermal stability and dispersion stability, can not generate obvious temperature interval change in the heating-cooling circulation process, and keep high dispersion of suspension. Based on the better photo-thermal property of the nano-crystalline gallium-indium particles, the nano-crystalline gallium-indium particles are a better photo-thermal treatment material and can be applied to photo-thermal treatment.
Experimental example 6
In this experimental example, the effect of the liquid metal nanoparticles in a rice form (gallium indium eutectic nanoparticles in a rice form) as a tumor photothermal therapeutic agent was examined, wherein the gallium indium eutectic nanoparticles in a rice form were prepared in example 1. The detection method comprises the following steps:
1. in vitro cytotoxicity assays
Inoculation of 10 in 96-well plates44T1 cells (mouse breast cancer cells) were cultured for 24 hours. Then, different concentrations (0, 50,100,250,500, 1000. mu.g/mL, 100. mu.L/well) of the in-Mi eutectic gallium nanoparticles were added and incubated for 4 hours. After PBS wash, incubation was continued with RPMI 1640 (50. mu.L) medium. Subsequently, a 808nm laser was used at a power intensity of 1.6W cm-2Next, the cells were continuously irradiated for 5 minutes. The control group was not irradiated with laser light. Finally, the cell viability was determined by CCK-8 kit.
The cytotoxicity of the indium gallium eutectic nanoparticle in a meter shape to 4T1 is determined by standard CCK-8. Inoculation of 6X 10 in 96-well plates3The cells were then mixed with different concentrations (50,100,250,500 and 1000. mu.g ml)-1) The indium gallium eutectic nanoparticles in the form of rice are incubated together for 24 hours, then washed 2 times with RPMI 1640 medium, and 10. mu.L of CCK-8 solution, 90. mu.L of RPMI 1640, are added to each well and incubated for 1 hour. Absorbance at 450nm was collected by a microplate reader (Infinite M200PRO, Tecan).
2. Calcein AM/PI staining
Inoculation of 10 in 96-well plates44T1 cells until the growth density reaches 80-90%. After PBS washing, 4T1 cells were incubated with the indium gallium-in-mil eutectic nanoparticles for 4 hours. The 4T1 cells were then washed 3 times with PBS, incubated in 200. mu.L of RPMI 1640 medium, and then laser irradiated (808nm, 1.6W cm)-2) For 5 minutes. 4T1 cells treated with the indium gallium eutectic nanoparticle in the form of a rice and laser irradiated alone were used as controls. After removal of the RPMI 1640 medium, live and dead cells were determined using the Calcein AM/PI kit.
3. Photothermal tumor excision in vivo
To model transplantable tumors, female BALB/c mice (6-week, Jackson laboratories) were used at 1X 1064T1 cells were seeded subcutaneously in the back. Tumor volume was about 90mm 5 days after tumor inoculation3. The mice are divided into four groups (group 1: the gallium indium eutectic nano particles in a meter shape + the laser, group 2: the gallium indium eutectic nano particles in a meter shape, group 3: the PBS + the laser, group4: PBS) (n ═ 6). The injection mode is intratumoral injection. In a typical photothermal therapy, 50 μ L of 0.5mg/mL of a gallium indium eutectic nanoparticle in a beige form is injected into a tumor in a mouse. Then, the tumor was continuously irradiated with laser light for 5 minutes (1.6W cm)-2). Tumors were subsequently monitored by bioluminescence and images were taken using the IVIS luminea imaging system (Perkin Elmer). The tumor size is measured by a vernier caliper, and the tumor volume (V) is calculated by the formula of V ═ L × W2L and W are the length and width of the tumor, respectively.
The detection results are as follows:
fig. 29 shows the cytotoxicity of the in-m-gallium-indium eutectic nanoparticles under irradiation with laser light and without irradiation with laser light. As can be seen from FIG. 29, when no laser is irradiated, even if the concentration of the indium gallium diselenide eutectic nanoparticle suspension is as high as 500. mu.g/mL, the cytotoxicity of the indium gallium diselenide eutectic nanoparticle to 4T1 cells is negligible. However, when the irradiation with the near-infrared laser of 808nm was continued for 5min (1.6W cm)-2) And (6) finally. More than 90% of the 4T1 cells were killed. FIG. 30 shows Calcein AM/PI staining patterns of 4T1 cells, in which Calcein AM reagent stains live cells and PI reagent stains dead cells; in the figure, while Nanorice indicates cells treated with only Mi-indium gallium eutectic nanoparticles, Laser indicates cells irradiated with only near-infrared Laser, and Nanorice + Laser indicates cells irradiated with near-infrared Laser after treated with Mi-indium gallium eutectic nanoparticles. As can be seen from fig. 30, substantially all of the gallium indium eutectic nanoparticles and laser irradiated 4T1 cells died, while most of the 4T1 cells remained viable when irradiated with either gallium indium eutectic nanoparticles or laser alone.
FIG. 31 shows a dynamic TEM image of the in-gallium eutectic nanoparticle in the form of a meter, on a ruler, at 100nm, under continuous laser irradiation. Wherein the laser wavelength is 808nm, and the power is 1.6W cm-2The continuous irradiation time was 5 min. As can be seen from fig. 31, the morphology of the in-gallium eutectic nanoparticle was well preserved during continuous laser irradiation (5 minutes) with no significant transformation.
FIG. 32 shows infrared thermographic images of mice under laser irradiation at different times, wherein EGaIn nanophase indicates intratumoral injectionAnd (3) shooting a mouse with the nano gallium-indium eutectic nano particles in a rice shape, wherein PBS represents a mouse injected with PBS in tumor. Two groups of mice were anesthetized and tumors were laser irradiated at 808nm (1.6W cm)-2) The real-time infrared thermography of the mice and the temperature change of the tumor area during the photothermal treatment were recorded every minute for 5 minutes, resulting in the results shown in fig. 32. As can be seen from FIG. 32, for the mice injected with the in-Ga eutectic nanoparticles in the form of rice, the temperature of the irradiated area increased significantly from 32.4 ℃ to-46.9 ℃ in 2 minutes and continuously increased to-50.3 ℃ in 5 minutes, which is sufficient to ablate tumors efficiently. In contrast, only the control group irradiated by laser obtained only a slight temperature rise (2.5 ℃) under the same conditions, which indicates that the nano gallium indium eutectic nanoparticle in the form of a meter can effectively convert light energy into heat energy, and the adopted laser irradiation conditions can not generate excessive heat in the thermal therapy, thereby avoiding damage to normal tissues.
Fig. 33 shows bioluminescence patterns of 4T1 tumor growth in mice treated with PBS, PBS and laser irradiation, and with gallium indium eutectic nanoparticles and laser irradiation, respectively, and it can be seen from fig. 33 that dark burning scars were generated at the tumor treated with gallium indium eutectic nanoparticles and laser irradiation, and no tumor was detected by bioluminescence after the treatment on day 8, indicating that the tumor was effectively ablated with gallium indium eutectic nanoparticles and laser irradiation.
Fig. 34 shows immunohistochemical staining patterns, scale bar, 200 μm of 4T1 tumor tissue in mice treated with indium gallium eutectic nanoparticles and laser irradiation, indium gallium eutectic nanoparticles treatment, PBS and scaffolding irradiation, and laser irradiation. As can be seen from fig. 34, the tumor tissue was effectively eliminated in the mice treated with the gallium-indium-gallium-nanoparticle in the form of a rice and the laser irradiation, and the results of the measurement were consistent with those in fig. 33.
FIG. 35 is a graph showing the results of tumor growth and survival status tests of mice in different treatment groups. Fig. 35a shows the tumor growth curves of mice in different treatment groups (n-6). Data are shown as mean ± standard deviation, # P <0.001, two-way ANOVA analyzed using Tukey post-hoc test. Fig. 35b shows survival curves for different treatment groups of mice (n ═ 6). Using Log-Rank (Mantel-Cox) assay, P < 0.001. As can be seen from fig. 35a and 35b, for the control group treated with the gallium indium eutectic nanoparticle in the form of mi or laser irradiation alone, the tumor volume rapidly increased, showing a similar trend to untreated mice (PBS alone), and all of these mice died within 27 days after the treatment, whereas with the gallium indium eutectic nanoparticle in the form of mi and laser irradiation treatment, after effectively ablating the tumor, no recurrence of the tumor was observed in the next 60 days, and the survival period of the mice was long. Figure 35c shows the body weight curves of mice in different treatment groups (n-6). Data are shown as mean ± standard deviation. As can be seen from FIG. 35, the gallium indium diselocrystal nanoparticle in the form of a nanoparticle as a photothermal therapeutic agent can effectively ablate tumors, and photothermal therapy does not result in significant weight loss, indicating that the gallium indium diselocrystal nanoparticle in the form of a nanoparticle has good biocompatibility.
According to the detection results, the meter-shaped gallium-indium eutectic nanoparticles can release heat after being excited by near-red light due to the good photo-thermal conversion efficiency, effectively ablate tumor tissues and have a good tumor treatment effect. Meanwhile, after tumor ablation, the prognosis is good, and long-term relapse prevention can be kept. The nanometer gallium-indium eutectic nanometer particle has low cytotoxicity, can be used for ablating tumor tissues, does not cause damage to normal tissues, does not obviously reduce the weight of mice, shows that the nanometer gallium-indium eutectic nanometer particle has high biocompatibility, and is a novel, effective and safe tumor photothermal therapeutic agent.
In the above examples and experimental examples, all the results are expressed as mean ± standard deviation. When more than two sets of data were compared (multiple comparisons), two-way analysis of variance (ANOVA) and Tukey post-hoc tests were used. All statistical analyses were performed using IBM SPSS statistical data 19. The threshold for statistical significance was P < 0.05.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims (15)

1. A method for synthesizing rice-shaped liquid metal nanoparticles, wherein the liquid metal is gallium-indium eutectic, is characterized by comprising the following steps:
preparing a mixed solution containing melanin nano particles and gallium-indium eutectic, and introducing inert gas into the mixed solution, wherein the concentration of the melanin nano particles in the mixed solution is 0.25mg/mL;
carrying out ultrasonic treatment on the mixed solution for more than or equal to 15min to obtain rice-shaped liquid metal nanoparticles; the ultrasonic treatment further comprises: the temperature of the mixed solution is controlled to be less than or equal to 60 ℃.
2. The synthesis method according to claim 1, wherein the step of preparing a mixed solution containing melanin nanoparticles and gallium-indium eutectic comprises: adding the melanin nanoparticles and the gallium-indium eutectic into a solvent to obtain a mixed solution containing the melanin nanoparticles and the gallium-indium eutectic, wherein the solvent is water, and the inert gas is argon.
3. The method of claim 1, wherein the melanin nanoparticles have a particle size of 2-4 nm.
4. The method of claim 2, wherein the melanin nanoparticles have a particle size of 2-4 nm.
5. The synthetic method according to any one of claims 1-4 wherein the step of preparing the melanin nanoparticles comprises:
carrying out acid-base treatment on the melanin granules to reduce the particle size of the melanin granules to a nanometer level so as to obtain a melanin nanoparticle solution;
and carrying out ultrafiltration, washing and drying treatment on the melanin nanoparticle solution to obtain the melanin nanoparticles.
6. The method of synthesis according to claim 5, wherein the acid-base treatment comprises: adding melanin particles into a sodium hydroxide solution to obtain a melanin solution, and adjusting the pH of the melanin solution to 7 by using a hydrochloric acid solution to obtain a melanin nanoparticle solution;
the ultrafiltration treatment has a molecular weight cut-off of 30 kDa.
7. The method of synthesis according to any one of claims 1-4, further comprising:
carrying out ultrasonic treatment on the mixed solution, removing the precipitate, and taking the upper layer slurry; and (3) carrying out centrifugal treatment on the slurry, and removing the precipitate to obtain a solution dispersed with the rice-shaped liquid metal nano particles.
8. The synthesis method according to claim 7, wherein the centrifugation treatment conditions are 1000rpm and the centrifugation time is 5 min.
9. A liquid metal nanoparticle in a rice form, characterized in that it is synthesized by the synthesis method according to any one of claims 1 to 8.
10. The rice-shaped liquid metal nanoparticle according to claim 9, wherein the liquid metal nanoparticle is a gallium indium eutectic nanoparticle, and the surface of the gallium indium eutectic nanoparticle is chelated with a melanin nanoparticle; the liquid metal nanoparticles have an aspect ratio of 2:1 to 3: 1.
11. The rice-shaped liquid metal nanoparticles of claim 10, wherein the liquid metal nanoparticles have an aspect ratio of 2.3.
12. Use of a liquid metal nanoparticle in a rice form synthesized by the synthesis method of any one of claims 1 to 8 in the preparation of a photothermal therapy material.
13. Use of a liquid metal nanoparticle in a rice form synthesized by the synthesis method of any one of claims 1 to 8 in the preparation of a reagent for treating a tumor.
14. A photothermal therapeutic agent comprising the rice-shaped liquid metal nanoparticles synthesized by the synthesis method according to any one of claims 1 to 8.
15. A kit for treating tumor, comprising the liquid metal nanoparticles in a rice form synthesized by the synthesis method according to any one of claims 1 to 8, or the photothermal therapeutic agent according to claim 14.
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