CN113845904A - Preparation of boron-nitrogen doped graphene quantum dots and application of boron-nitrogen doped graphene quantum dots in boron neutron capture treatment drugs - Google Patents
Preparation of boron-nitrogen doped graphene quantum dots and application of boron-nitrogen doped graphene quantum dots in boron neutron capture treatment drugs Download PDFInfo
- Publication number
- CN113845904A CN113845904A CN202111231001.3A CN202111231001A CN113845904A CN 113845904 A CN113845904 A CN 113845904A CN 202111231001 A CN202111231001 A CN 202111231001A CN 113845904 A CN113845904 A CN 113845904A
- Authority
- CN
- China
- Prior art keywords
- boron
- graphene quantum
- doped graphene
- nitrogen doped
- quantum dots
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- TZHYBRCGYCPGBQ-UHFFFAOYSA-N [B].[N] Chemical compound [B].[N] TZHYBRCGYCPGBQ-UHFFFAOYSA-N 0.000 title claims abstract description 72
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 229910052796 boron Inorganic materials 0.000 title claims abstract description 27
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 16
- 229940079593 drug Drugs 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 45
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 45
- 239000002096 quantum dot Substances 0.000 claims abstract description 41
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 40
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000004327 boric acid Substances 0.000 claims abstract description 18
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 39
- 229910021389 graphene Inorganic materials 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 16
- 238000004108 freeze drying Methods 0.000 claims description 15
- 239000000843 powder Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 210000004881 tumor cell Anatomy 0.000 claims description 13
- 229940124447 delivery agent Drugs 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- 229920002472 Starch Polymers 0.000 claims description 7
- 238000001027 hydrothermal synthesis Methods 0.000 claims description 7
- 235000019698 starch Nutrition 0.000 claims description 7
- 239000008107 starch Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000007740 vapor deposition Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 230000008685 targeting Effects 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000003745 diagnosis Methods 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 5
- 230000003287 optical effect Effects 0.000 abstract description 4
- -1 graphite alkene Chemical class 0.000 abstract description 3
- 231100000053 low toxicity Toxicity 0.000 abstract description 3
- 229910002804 graphite Inorganic materials 0.000 abstract 2
- 239000010439 graphite Substances 0.000 abstract 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000004060 metabolic process Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 48
- 210000001519 tissue Anatomy 0.000 description 16
- 230000000694 effects Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 6
- 230000004992 fission Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 238000004043 dyeing Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010020843 Hyperthermia Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 230000036031 hyperthermia Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 238000012984 biological imaging Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229910010277 boron hydride Inorganic materials 0.000 description 1
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000012634 optical imaging Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000007903 penetration ability Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/65—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing carbon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/009—Neutron capture therapy, e.g. using uranium or non-boron material
- A61K41/0095—Boron neutron capture therapy, i.e. BNCT, e.g. using boronated porphyrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Inorganic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Optics & Photonics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- Manufacturing & Machinery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses preparation of boron-nitrogen doped graphene quantum dots and application of the boron-nitrogen doped graphene quantum dots in boron neutron capture treatment drugs, and relates to the field of chemical and biomedical tumor diagnosis and treatment. Which is prepared from graphene quantum dots and10b boric acid aqueous solution is used as a raw material to synthesize the boron-nitrogen doped graphene quantum dots, the boron-nitrogen doped graphene quantum dots have high boron content, excellent optical properties, good biocompatibility and low toxicity, and in-vivo fluorescence formation is realizedLike this, can also target breast cancer tumour and enrich in breast cancer tumour position, but boron nitrogen doping graphite alkene quantum dot can be excreted by the rapid metabolism in healthy tissue, and these properties make boron nitrogen doping graphite alkene quantum dot can be regarded as a novel boron transport agent who is applicable to BNCT treatment, realize the diagnosis and the BNCT treatment to breast cancer tumour.
Description
Technical Field
The invention relates to the field of chemical and biomedical tumor diagnosis and treatment, in particular to preparation of boron-nitrogen doped graphene quantum dots and application of the boron-nitrogen doped graphene quantum dots in boron neutron capture treatment medicines.
Background
Boron Neutron Capture Therapy (BNCT) as a novel precise tumor therapy by intracellular localization in tumor cells10B captures thermal neutrons to generate alpha particles by nuclear fission reaction7Li recoils the nucleus, selectively killing the tumor cells. BNCT is based on nuclear capture and nuclear fission reactions, due to non-radioactivity10B atoms (the content of the B atoms in natural boron element is 20 percent) can generate neutron capture and further generate nuclear fission,10b is activated after being irradiated by neutrons of a certain energy11B and subsequently split into high-energy alpha particles and7li recoil nucleus, the nuclear reaction formula is:
B10+nth→[B11]*→α+Li7+2.31MeV
high energy alpha particles and7li recoil nucleus can be dissociated in the micro-space (about 5-9 μm) of the diameter of target (cell) at the instant of reaction. Since the lethal intensity of the capture reaction is limited by the boron-containing cells, BNCT can be considered as a biological and physical targeted radiation therapy, wherein the success or failure of BNCT depends on whether the tumor takes up sufficient amounts of the tumor10B, i.e. ensuring that a sufficient amount of10B is selectively delivered to the interior of tumor cells and reduces the absorption of normal tissues of human body near the tumor as much as possible10And B, avoiding the damage of the normal tissues of the human body caused by nuclear capture and nuclear fission reaction.
The artificial synthesized boron conveying extrusion has more varieties, but can be used for clinical treatment at presentOnly two of them: one is polyhedral boron hydride anion, also known as sodium boron clathrate or BSH (Na)2B12H11SH), used mainly in japan; the other is a dihydroxyborophenylalanine derivative, also known as borocagophenylalanine or BPA, used in clinical trials mainly in the United states, Europe, Japan, Argentina, and tortuosity, among others. Both BPA and BSH were administered intravenously and neutron irradiation was performed on tumor foci, with the neutron source being provided by a specially adapted nuclear reactor. By 1994, Japan used mainly Low energy (<0.5eV), because of the limited penetration depth of low-energy thermal neutron beam to human tissue, the subsequent us, europe and japan adopted the hyperthermia neutron beam (the energy of the hyperthermia neutron is 0.5eV to 10keV) with stronger penetration ability and stronger energy in clinical trial.
Theoretically, BNCT is highly selective, and can not cause radiation damage to normal cells and tissues around a tumor by taking tumor cells as targets, compared with the conventional external beam photon radiation therapy which needs to be carried out for 6-7 weeks, the dosage of 60-70 Gy can be delivered into the tumor cells in 1-2 administration time periods by the BNCT. However, the effectiveness of BNCT depends on10The relative uniformity of B distribution in tumors, which is still an unsolved problem in BNCT, has limited the development of BNCT.
Meanwhile, BNCT boron delivery agents still remain a difficult problem to be solved urgently at present. The most important requirements for boron delivery agents are: 1. the toxicity of the whole body of the human body is low, the intake of the normal tissues of the human body is low, and the intake of the tumor cells is higher along with the increase of the malignancy of the tumor cells, namely the higher the malignancy of the tumor cells is. 2. The concentration of boron delivery agent in the tumor was 2010B/g. 3. The boron delivery agent is rapidly cleared from the patient's blood and normal tissues during BNCT, but persists within the tumor. However, there are currently no boron transporters that simultaneously meet the above requirements. Therefore, there is an urgent need to find a boron-containing complex as an effective boron delivery agent, which can significantly increase the water solubility of highly lipid-soluble drugs, slow down the half-life of the drugs, and improve the bioavailability.
Disclosure of Invention
The invention aims to solve the problems and provides a preparation method of boron-nitrogen doped graphene quantum dots and application of the boron-nitrogen doped graphene quantum dots in boron neutron capture treatment drugs.
In order to achieve the purpose, the invention adopts the following technical scheme:
boron-nitrogen doped graphene quantum dot, graphene quantum dot and preparation method thereof10B boric acid water solution is used as a raw material, wherein the graphene quantum dots and the graphene quantum dots10The mass ratio of the boric acid aqueous solution B is 1: 2.
Preferably, the particle size of the boron-nitrogen doped graphene quantum dot is 40-70 nm.
According to the preparation method of the boron-nitrogen doped graphene quantum dot, the boron-nitrogen doped graphene quantum dot is synthesized by adopting a vapor deposition method.
Preferably, the method specifically comprises the following steps:
a. dissolving soluble starch in water, mixing and stirring to obtain a solution, adding the solution into a reaction kettle to perform hydrothermal reaction to obtain a reaction solution, centrifuging and filtering the reaction solution, and freeze-drying the upper layer solution to obtain graphene quantum dot powder;
b. mixing graphene quantum dot powder with10B, uniformly mixing the boric acid aqueous solution, freeze-drying to obtain a powdery product, placing the powdery product in a tube furnace, and introducing NH into the tube furnace3Carrying out reaction to obtain boron-nitrogen doped graphene quantum dots;
c. and washing the boron-nitrogen doped graphene quantum dots in hot water, and freeze-drying to obtain boron-nitrogen doped graphene quantum dot powder.
Preferably, in the step a, the set temperature of the reaction kettle is 150-200 ℃, and the hydrothermal reaction time is 60-120 min.
Preferably, the10The concentration of the boric acid aqueous solution B is 0.1-1 mg/mL,10b in an aqueous solution of boric acid10Of BThe abundance ratio is 95%.
Preferably, in the step b, the set temperature of the tube furnace is 700-900 ℃.
The boron-nitrogen doped graphene quantum dot is applied to tumor BNCT treatment medicines.
Preferably, the use comprises targeting breast cancer tumor tissue and enriching at the breast cancer tumor site.
Preferably, the application comprises as a boron delivery agent10B is delivered to tumor cells.
The invention has the beneficial effects that:
the invention constructs a graphene quantum dot and10the B boric acid aqueous solution is used as a raw material to synthesize the boron-nitrogen doped graphene quantum dots (BNGO), and the boron-nitrogen doped graphene quantum dots have excellent optical properties, good biocompatibility and low toxicity, and have important application prospects in the fields of biological imaging, chemical sensing, photocatalysis, drug delivery and the like. Experiments prove that the graphene quantum dots and the graphene quantum dots are used in the invention10The BNGO synthesized by using the boric acid B aqueous solution as a raw material can target breast cancer tumors and is enriched at the breast cancer tumor parts, and the BNGO in healthy tissues can be rapidly metabolized and excreted, thereby providing conditions for realizing BNCT treatment. Therefore, BNGO can be used as a novel boron delivery agent suitable for BNCT treatment to realize the diagnosis of breast cancer tumors and BNCT treatment.
Drawings
FIG. 1 is a schematic drawing of a BNGO nanoparticle atomic particle microscope AFM of the present invention.
FIG. 2 is a fluorescence emission spectrum of BNGOs of the present invention.
FIG. 3 is a graph showing the effect of BNGO on survival of breast cancer cells 4T 1.
Fig. 4 is a schematic representation of the cell morphology of breast cancer cells without BNGO after neutron irradiation.
Fig. 5 is a schematic diagram of cell morphology of breast cancer cells containing BNGO after neutron irradiation.
FIG. 6 shows the results of a control experiment observed with an optical microscope under C1-203; panel (a) shows breast cancer cells containing BNGO and panel (b) shows breast cancer cells without BNGO.
FIG. 7 is a graph showing the effect of BNGO on the number of monoclonal cells.
FIG. 8 is an ex vivo graph of mouse major organs and breast cancer tumor model after BNGO injection.
Detailed Description
The invention provides a preparation method of boron-nitrogen doped graphene quantum dots and application of the boron-nitrogen doped graphene quantum dots in boron neutron capture treatment drugs, and in order to make advantages and technical schemes of the invention clearer and clearer, the invention is described in detail with specific embodiments.
The raw materials required by the invention can be purchased from commercial sources.
The invention relates to graphene quantum dots and10b boric acid aqueous solution is used as a raw material to synthesize boron-nitrogen doped graphene quantum dots (BNGO), graphene quantum dots and graphene quantum dots10The mass ratio of the boric acid aqueous solution B is 1:2, wherein the graphene quantum dots are prepared by using soluble starch and water as raw materials, the soluble starch has no reducing substances, stable chemical properties and strong adsorption force, and the flowability of the medicament can be obviously improved. Meanwhile, a large amount of nutrients are needed for the rapid propagation of tumor cells, and the boron-nitrogen doped graphene quantum dots enter the tumor cells through the endocytosis of the tumor cells.
The boron-nitrogen doped graphene quantum dot (BNGO) provided by the invention has excellent optical properties, good biocompatibility and low toxicity, the particle size of the boron-nitrogen doped graphene quantum dot is 40-70 nm, because the solid tumor tissue has abundant blood vessels, wider vascular wall gaps and complete structure, and lymphatic return is absent, based on EPR effect, BNGO can be enriched in the tumor tissue, and conversely, because the capillary endothelium gaps in the healthy tissues of the human body are compact and the structure is complete, and the macromolecules and the straight particles are not easy to permeate through the vascular wall, the distribution of the BNGO in the normal tissues of the human body is reduced, therefore, the BNGO provided by the invention can target tumor tissues, in particular breast cancer tumor tissue, and is enriched at the tumor part without influencing the healthy tissue of the human body, has passive targeting to tumor tissues, is suitable for a novel boron delivery agent for BNCT treatment, and realizes the diagnosis of tumors and BNCT treatment.
The preparation method of the boron-nitrogen doped graphene quantum dot of the invention is explained in detail below.
Example 1:
the boron-nitrogen doped graphene quantum dot provided by the invention is synthesized by adopting a vapor deposition method, and the preparation method specifically comprises the following steps:
a. dissolving 0.25g of soluble starch in 25ml of water, mixing and stirring to obtain a dissolved solution, adding the dissolved solution into a reaction kettle at the temperature of 190 ℃ to perform hydrothermal reaction for 120min to obtain a reaction solution, centrifuging and filtering the reaction solution, removing lower-layer solids in the reaction solution, and then taking an upper-layer solution to perform freeze drying to obtain graphene quantum dot powder;
b. 0.1g of graphene quantum dot powder and 100ml10B aqueous boric acid solution (concentration 1 mg/mL),10The abundance of B is 95 percent), freeze-drying to obtain a powdery product, putting the powdery product into a tube furnace, setting the temperature of the tube furnace to 900 ℃, and introducing NH into the furnace3Carrying out reaction to obtain boron-nitrogen doped graphene quantum dots;
c. and washing the boron-nitrogen doped graphene quantum dots in hot water for multiple times, and freeze-drying to obtain boron-nitrogen doped graphene quantum dot powder.
The boron-nitrogen doped graphene quantum dot framework prepared by the method disclosed by the invention has the advantages that the content of boron is about 20%, the content of nitrogen is about 20%, the content of boron is high, and the particle size of the boron-nitrogen doped graphene quantum dot is 40-70 nm, as shown in figure 1.
The breast cancer cells and BNGOs are selected for culture, and the result shows that BNGO can enter the breast cancer cells in a targeted mode, the fluorescence imaging effect of the breast cancer cells based on BNGO is observed under a fluorescence microscope, and the fluorescence emission spectrum of BNGOs is shown in FIG. 2.
BNGO has good fluorescence characteristic, when receiving 350 ~ 380nm exciting light excitation, can send green fluorescence between 420 ~ 530nm, because BNGO can both excite stronger fluorescence under the excitation wavelength of difference, so BNGO is applicable to the quantitative analysis of cellular optical imaging.
Example 2
In order to verify the application effect of the boron-nitrogen doped graphene quantum dot prepared in example 1 in the BNCT treatment process, human breast cancer cells 4T1 and BNGOs were selected for culture, and the results show that BNGOs can enter the breast cancer cells in a targeted manner and perform fluorescence imaging.
The effect of BNGO on survival of breast cancer cells 4T1 as shown in figure 3, IC50 of breast cancer cells 4T1 after BNCT treatment was 176.45 ug/mL.
In the experimental process, the cell morphology of the breast cancer cell containing the boron-nitrogen doped graphene quantum dots and the cell morphology of the breast cancer cell not containing the boron-nitrogen doped graphene quantum dots after 24 hours of single BNCT treatment are observed, and fig. 4 shows the cell morphology of the breast cancer cell not containing the boron-nitrogen doped graphene quantum dots after neutron irradiation, so that the breast cancer cell not incubated by BNGO medicines is still full and has good extensibility, the proliferation condition is good, and the cell nucleus and cytoplasm are normal. Fig. 5 shows the cell morphology of the breast cancer cell containing boron-nitrogen doped graphene quantum dots after neutron irradiation, and it can be seen that the breast cancer cell incubated by the BNGO drug has rounded cells after neutron irradiation, cannot grow normally adherent, has abnormal cell morphology and is difficult to observe the cell nucleus, so that the BNGO can be used for significantly inhibiting the breast cancer cell in BNCT treatment.
Example 3
In order to study the effect of the boron-nitrogen doped graphene quantum dots prepared in example 1 on the monoclonal antibody of breast cancer cells 4T 1. Setting a contrast experiment, culturing cultured breast cancer cells 4T1 and BNGOs in an experimental group of the contrast experiment, incubating for 24h, then suspending the cells in a culture medium, irradiating for 1h through a neutron flow of an accelerator, then transplanting the cells into the culture medium again for culture, recording the number of the breast cancer cells 4T1 by using a cell counting plate, culturing the irradiated breast cancer cells 4T1 in the culture medium for 7 days, dyeing the breast cancer cells 4T1 in the culture medium by adopting a crystal violet dyeing method, counting the number of the breast cancer cells 4T1 in the culture medium at the moment, and since the crystal violet can dye cytoplasm of the cells, the number of the cells can be determined by observing the dyeing area of the culture medium. To be betterVerifying the influence of BNGO on breast cancer cells 4T1, and the experiment is also provided with a control group, wherein the control group is not cultured with BNGOs except for breast cancer cells 4T1, and the rest experiment conditions and operations are the same as those of the experiment group. The control experiment results are shown in fig. 6 and 7, the experiment results verify that the boron-nitrogen doped graphene quantum dots can influence the monoclonal cell number of breast cancer cells 4T1, and after the boron-nitrogen doped graphene quantum dots are added into a culture dish according to 200ug/mL and incubated for 24 hours, every 10 hours5The content of boron which can be phagocytized by the breast cancer cells 4T1 is about 20-40 ug.
Example 4
In order to verify that the boron-nitrogen doped graphene quantum dots prepared in example 1 have a good targeting effect on breast cancer tumors. The axillary mammary gland fat pad planted with common cells is used as a breast cancer tumor model of a mouse, and the dosage of boron-nitrogen doped graphene quantum dots is 200mg per kilogram according to the weight of the mouse. Injecting the boron-nitrogen doped graphene quantum dots into a mouse body through rat tail vein injection, and after injection for 4h, dissecting and observing the distribution of the boron-nitrogen doped graphene quantum dots in each organ of the mouse, wherein the boron-nitrogen doped graphene quantum dots obtained through observation have a tumor targeted enrichment function, can be enriched and subjected to luminescence imaging at a breast cancer tumor, realize quantitative imaging monitoring of a drug at the breast cancer tumor part, and are beneficial to improvement of a BNCT treatment effect, as shown in figure 8.
Example 5
The boron-nitrogen doped graphene quantum dot provided by the invention is synthesized by adopting a vapor deposition method, and the preparation method specifically comprises the following steps:
a. dissolving 0.25g of soluble starch in 25ml of water, mixing and stirring to obtain a dissolved solution, adding the dissolved solution into a reaction kettle at the temperature of 200 ℃ for hydrothermal reaction for 60min to obtain a reaction solution, centrifuging and filtering the reaction solution, removing lower-layer solids in the reaction solution, and freeze-drying the upper-layer solution to obtain graphene quantum dot powder;
b. 0.1g of graphene quantum dot powder and 100ml10B aqueous boric acid solution (concentration 0.1 mg/mL),10The abundance of B is 95 percent), and then freeze-drying to obtain a powdery productPlacing the product in a tube furnace, setting the temperature of the tube furnace at 700 ℃, and introducing NH into the furnace3Carrying out reaction to obtain boron-nitrogen doped graphene quantum dots;
c. and washing the boron-nitrogen doped graphene quantum dots in hot water for multiple times, and freeze-drying to obtain boron-nitrogen doped graphene quantum dot powder.
Example 6
The boron-nitrogen doped graphene quantum dot provided by the invention is synthesized by adopting a vapor deposition method, and the preparation method specifically comprises the following steps:
a. dissolving 0.25g of soluble starch in 25ml of water, mixing and stirring to obtain a dissolved solution, adding the dissolved solution into a reaction kettle at the temperature of 150 ℃ to perform hydrothermal reaction for 100min to obtain a reaction solution, centrifuging and filtering the reaction solution, removing lower-layer solids in the reaction solution, and then taking an upper-layer solution to perform freeze drying to obtain graphene quantum dot powder;
b. 0.1g of graphene quantum dot powder and 100ml10B aqueous boric acid solution (concentration 0.5 mg/mL),10The abundance of B is 95 percent), freeze-drying to obtain a powdery product, putting the powdery product into a tube furnace, setting the temperature of the tube furnace to be 800 ℃, and introducing NH into the furnace3Carrying out reaction to obtain boron-nitrogen doped graphene quantum dots;
c. and washing the boron-nitrogen doped graphene quantum dots in hot water for multiple times, and freeze-drying to obtain boron-nitrogen doped graphene quantum dot powder.
The parts which are not described in the invention can be realized by taking the prior art as reference.
It should be noted that: any equivalents or obvious modifications thereof which may occur to persons skilled in the art and which are given the benefit of this description are deemed to be within the scope of the invention.
Claims (10)
1. The boron-nitrogen doped graphene quantum dot is characterized by comprising the following components in parts by weight10B boric acid water solution is used as a raw material, wherein the graphene quantum dots and the graphene quantum dots10The mass ratio of the boric acid aqueous solution B is 1: 2.
2. The boron-nitrogen doped graphene quantum dot according to claim 1, wherein the particle size of the boron-nitrogen doped graphene quantum dot is 40-70 nm.
3. The method for preparing the boron-nitrogen-doped graphene quantum dot according to claim 1, wherein the boron-nitrogen-doped graphene quantum dot is synthesized by a vapor deposition method.
4. The method for preparing the boron-nitrogen doped graphene quantum dot according to claim 3, which is characterized by comprising the following steps:
a. dissolving soluble starch in water, mixing and stirring to obtain a solution, adding the solution into a reaction kettle to perform hydrothermal reaction to obtain a reaction solution, centrifuging and filtering the reaction solution, and freeze-drying the upper layer solution to obtain graphene quantum dot powder;
b. mixing graphene quantum dot powder with10B, uniformly mixing the boric acid aqueous solution, freeze-drying to obtain a powdery product, placing the powdery product in a tube furnace, and introducing NH into the tube furnace3Carrying out reaction to obtain boron-nitrogen doped graphene quantum dots;
c. and washing the boron-nitrogen doped graphene quantum dots in hot water, and freeze-drying to obtain boron-nitrogen doped graphene quantum dot powder.
5. The method for preparing the boron-nitrogen doped graphene quantum dot according to claim 4, wherein in the step a, the set temperature of the reaction kettle is 150-200 ℃, and the hydrothermal reaction time is 60-120 min.
6. The method for preparing boron-nitrogen doped graphene quantum dots according to claim 4, wherein the method is characterized in that10The concentration of the boric acid aqueous solution B is 0.1-1 mg/mL,10b in an aqueous solution of boric acid10The abundance of B was 95%.
7. The method for preparing boron-nitrogen doped graphene quantum dots according to claim 4, wherein in the step b, the set temperature of the tube furnace is 700-900 ℃.
8. The application of the boron-nitrogen doped graphene quantum dot according to claim 1 in tumor BNCT treatment medicines.
9. The use of boron-nitrogen doped graphene quantum dots in a medicament for BNCT treatment of tumors according to claim 8, wherein the use comprises targeting breast cancer tumor tissue and enriching at breast cancer tumor sites.
10. The use of boron-nitrogen doped graphene quantum dots in tumor BNCT treatment drugs according to claim 8, wherein the use comprises using the boron-nitrogen doped graphene quantum dots as a boron delivery agent10B is delivered to tumor cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111231001.3A CN113845904B (en) | 2021-10-22 | 2021-10-22 | Preparation of boron-nitrogen doped graphene quantum dots and application of boron-nitrogen doped graphene quantum dots in boron neutron capture therapeutic drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111231001.3A CN113845904B (en) | 2021-10-22 | 2021-10-22 | Preparation of boron-nitrogen doped graphene quantum dots and application of boron-nitrogen doped graphene quantum dots in boron neutron capture therapeutic drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113845904A true CN113845904A (en) | 2021-12-28 |
| CN113845904B CN113845904B (en) | 2023-02-21 |
Family
ID=78982805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111231001.3A Expired - Fee Related CN113845904B (en) | 2021-10-22 | 2021-10-22 | Preparation of boron-nitrogen doped graphene quantum dots and application of boron-nitrogen doped graphene quantum dots in boron neutron capture therapeutic drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113845904B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101944640A (en) * | 2009-01-06 | 2011-01-12 | 凹凸电子（武汉）有限公司 | Battery management system and its transmission method |
| CN110294471A (en) * | 2019-06-27 | 2019-10-01 | 西北师范大学 | A kind of synthetic method of the nitrogen co-doped graphene quantum dot of boron |
| CN111204736A (en) * | 2020-01-09 | 2020-05-29 | 中国科学院高能物理研究所 | Preparation of boron-containing carbon quantum dots and application of boron-containing carbon quantum dots in medicines for tumor diagnosis and boron neutron capture treatment |
-
2021
- 2021-10-22 CN CN202111231001.3A patent/CN113845904B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101944640A (en) * | 2009-01-06 | 2011-01-12 | 凹凸电子（武汉）有限公司 | Battery management system and its transmission method |
| CN110294471A (en) * | 2019-06-27 | 2019-10-01 | 西北师范大学 | A kind of synthetic method of the nitrogen co-doped graphene quantum dot of boron |
| CN111204736A (en) * | 2020-01-09 | 2020-05-29 | 中国科学院高能物理研究所 | Preparation of boron-containing carbon quantum dots and application of boron-containing carbon quantum dots in medicines for tumor diagnosis and boron neutron capture treatment |
Non-Patent Citations (2)
| Title |
|---|
| GIANNI CIOFANI: "Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy", 《NANOSCALE RESEARCH LETTERS》 * |
| PAVITER SINGH: "Fluorescent boron carbide quantum dots synthesized with a low-temperature solvothermal approach for boron neutron capture therapy", 《PHYSICA E: LOW-DIMENSIONAL SYSTEMS AND NANOSTRUCTURES》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113845904B (en) | 2023-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hosmane | Boron and gadolinium neutron capture therapy for cancer treatment | |
| WO2021169744A1 (en) | Fluorescent carbon quantum dot, and preparation method therefor and application thereof in preparation of antitumor drug sensitizer | |
| CN111603559A (en) | Copper iodophor compound @ photosensitizer composite nanoparticle and application thereof as X-ray photodynamic therapy medicine | |
| CN111714631B (en) | Near-infrared driven self-oxygen supply compound and preparation method and application thereof | |
| CN114848854B (en) | The method comprises the following steps of 131 I-HSA-ICG nano-particle and preparation method and application thereof | |
| CN104984341B (en) | A kind of preparation method of the composite Nano preparation of near-infrared laser triggering | |
| CN110327359B (en) | Application of phenylboronic acid in preparation of cell nucleus targeted boron capture agent | |
| CN112979686B (en) | Novel boron carrier, preparation method and pharmaceutical preparation thereof | |
| CN107715110B (en) | Biodegradable black phosphorus-based X-ray photodynamic therapy photosensitizer and preparation method and application thereof | |
| CN107213479B (en) | A kind of composition and purposes comprising catalase | |
| CN108785672A (en) | A kind of nanoparticle-photosensitizer coupled system of novel excitation of X-rays photodynamic therapy deep tumor and its application | |
| CN111286326B (en) | Preparation method and application of silicate long-afterglow probe | |
| CN113845904B (en) | Preparation of boron-nitrogen doped graphene quantum dots and application of boron-nitrogen doped graphene quantum dots in boron neutron capture therapeutic drugs | |
| CN106606783B (en) | A kind of targeting is passed altogether to be released the drug of photosensitizer and chemotherapeutics and passs release system | |
| CN111204736B (en) | Preparation of boron-containing carbon quantum dots and application of boron-containing carbon quantum dots in medicines for tumor diagnosis and boron neutron capture treatment | |
| CN114617963A (en) | Synthesis method of gold nano-drug for targeted killing of tumor cells through cooperation of autophagy inhibition and photothermal therapy | |
| CN107998394A (en) | A kind of Performances of Novel Nano-Porous grain of rice-photosensitizer coupled system of excitation of X-rays photodynamic therapy deep tumor and preparation method thereof | |
| US20040213737A1 (en) | Radioactive arsenic-containing compounds and their uses in the treatment of tumors | |
| CN113750251A (en) | Multifunctional nano-drug carrier, and preparation method and application of therapeutic drug | |
| CN109806404B (en) | Albumin nanoparticle capable of achieving two-stage oxygen delivery and preparation method and application thereof | |
| CN108421041B (en) | Photodynamic therapy compound and preparation method and application thereof | |
| CN113274398B (en) | Nano self-assembly material for inhibiting tumor cell glycometabolism and preparation method and application thereof | |
| CN110279858A (en) | A kind of boracic preparation and its preparation method and application having cell nucleus targeting | |
| CN112972677B (en) | Porous magnetic diagnosis and treatment agent, preparation method and application | |
| CN118304277B (en) | Multi-response composite nano drug delivery system based on calcium-manganese oxide and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20230221 |