Nothing Special   »   [go: up one dir, main page]
Skip to main content
Springer Nature Link
Log in

MPEG-phenylboronic acid modified doxorubicin as the efficient pathological pH-responsive nanoplatform for potential anti-cancer delivery

  • Article
  • Published:
Macromolecular Research Aims and scope Submit manuscript

Abstract

Chemotherapy is the main strategy for inhibiting the tumor growth. However, during the therapy, the side effect of anti-cancer drug will injure normal cells. For reducing the toxic of the free drug, stimuli responsive nanoparticles (NPs) have been prepared base on the pathological acidic environment around tumor for safe and efficient anti-tumor applications. In this study, we fabricated the phenylboronic acid (PBA) modified monomethoxy polyethylene glycol (MEPG) for encapsulating doxorubicin (DOX NPs). In the drug delivery system (DDS), the pH-responsive boric ester could be stable during drug delivery, and enhance DOX rapidly release in tumor lesion under the acidic stimuli. In vitro studies further demonstrated that DOX NPs could efficiently endocytose by tumor cells, and exhibit the similar anti-tumor activity as the free DOX resulting from the pH-responsive drug release profiles under tumor acidic stimuli. In summary, DOX NPs could be a feasible candidate to improve the safe and efficient DOX delivery for improving the potential anti-tumor applications.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Explore related subjects

Discover the latest articles, news and stories from top researchers in related subjects.

References

  1. L. Zhu, Y. Zhong, S. Wu, M. Yan, Y. Cao, N. Mou, G. Wang, D. Sun, W. Wu, Cell membrane camouflaged biomimetic nanoparticles: Focusing on tumor theranostics. Mater. Today. Bio. 14, 100228 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. L. Liu, R. Wang, C. Wang, J. Wang, L. Chen, J. Cheng, Light-triggered release of drug conjugates for an efficient combination of chemotherapy and photodynamic therapy. Biomater. Sci. 6, 5 (2018)

    Article  Google Scholar 

  3. C. Friesen, I. Herr, P.H. Krammer, K.M. Debatin, Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat. Med. 2, 5 (1996)

    Article  Google Scholar 

  4. H.M. Kuerer, L.A. Newman, T.L. Smith, F.C. Ames, K.K. Hunt, K. Dhingra, R.L. Theriault, G. Singh, S.M. Binkley, N. Sneige, T.A. Buchholz, M.I. Ross, M.D. McNeese, A.U. Buzdar, G.N. Hortobagyi, S.E. Singletary, Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J. Clin. Oncol. 17, 2 (1999)

    Article  Google Scholar 

  5. F.M. Muggia, J.D. Hainsworth, S. Jeffers, P. Miller, S. Groshen, M. Tan, L. Roman, B. Uziely, L. Muderspach, A. Garcia, A. Burnett, F.A. Greco, C.P. Morrow, L.J. Paradiso, L.J. Liang, Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J. Clin. Oncol. 15, 3 (1997)

    Article  Google Scholar 

  6. O. Tacar, P. Sriamornsak, C.R. Dass, Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J. Pharm. Pharmacol. 65, 2 (2013)

    Google Scholar 

  7. X. Shuai, H. Ai, N. Nasongkla, S. Kim, J. Gao, Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. J. Control. Release. Off: J. Control. Release Soc. 98, 3 (2004)

    Google Scholar 

  8. D. Kim, E.S. Lee, K. Park, I.C. Kwon, Y.H. Bae, Doxorubicin loaded pH-sensitive micelle: antitumoral efficacy against ovarian A2780/DOXR tumor. Pharm. Res. 25, 9 (2008)

    Article  Google Scholar 

  9. J. Liu, D. Tu, J. Dancey, L. Reyno, K.I. Pritchard, J. Pater, L.K. Seymour, Quality of life analyses in a clinical trial of DPPE (tesmilifene) plus doxorubicin versus doxorubicin in patients with advanced or metastatic breast cancer: NCIC CTG Trial MA.19. Breast. Cancer. Res. Treat. 100, 3 (2006)

    Article  Google Scholar 

  10. R. Langer, D.A. Tirrell, Designing materials for biology and medicine. Nature 428, 6982 (2004)

    Article  Google Scholar 

  11. Y. Minamitake, R. Gref, M.T. Peracchia, V. Trubetskoy, V. Torchilin, R. Langer, Biodegradable long-circulating polymeric nanospheres. Science 263, 1600–1603 (1994)

    Article  PubMed  Google Scholar 

  12. B-BC Youan, Impact of nanoscience and nanotechnology on controlled drug. Nanomedicine, 3 (2008)

  13. J. Chan, L. Zhang, F.X. Gu, J.-W. Rhee, A.Z. Wang, A.F. Radovic-Moreno et al., Self assembled lipid-polymer hybrid nanoparticles a robust drug delivery. ACS Nano 2, 1696–1702 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  14. F. Alexis, E.M. Pridgen, R. Langer, O.C. Farokhzad, Nanoparticle technologies for cancer therapy. Handbook. Exp. Pharmacol. 197 (2010)

  15. O.C. Farokhzad, R. Langer, Impact of nanotechnology on drug delivery. ACS Nano 3, 1 (2009)

    Article  Google Scholar 

  16. C. Sun, L. Zhou, M. Gou, S. Shi, T. Li, J. Lang, Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles. Oncol. Rep. 35, 6 (2016)

    Article  Google Scholar 

  17. J.Z. Du, X.J. Du, C.Q. Mao, J. Wang, Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. J. Am. Chem. Soc. 133, 44 (2011)

    Article  Google Scholar 

  18. X. Li, B.Y. Zheng, M.R. Ke, Y. Zhang, J.-D. Huang, J. Yoon, A tumor-pH-responsive supramolecular photosensitizer for activatable photodynamic therapy with minimal in vivo skin phototoxicity. Theranostics. 7, 10 (2017)

    Article  CAS  Google Scholar 

  19. J. Liao, H. Zheng, Z. Fei, B. Lu, H. Zheng, D. Li, X. Xiong, Y. Yi, Tumor-targeting and pH-responsive nanoparticles from hyaluronic acid for the enhanced delivery of doxorubicin. Int. J. Biological. Macromol. 113, 737–747 (2018)

    Article  CAS  Google Scholar 

  20. H. Ma, Y. Liu, M. Shi, X. Shao, W. Zhong, W. Liao, M.M.Q. Xing, Theranostic, pH-responsive, doxorubicin-loaded nanoparticles inducing active targeting and apoptosis for advanced gastric cancer. Biomacromol 16, 12 (2015)

    Article  Google Scholar 

  21. X. Zhang, M. Zhao, N. Cao, W. Qin, M. Zhao, J. Wu, D. Lin, Construction of a tumor microenvironment pH-responsive cleavable PEGylated hyaluronic acid nano-drug delivery system for colorectal cancer treatment. Biomater, Science. 8, 7 (2020)

    Google Scholar 

  22. W. Wu, L. Luo, Y. Wang, Q. Wu, H.B. Dai, J.S. Li, C. Durkan, N. Wang, G.-X. Wang, Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications. Theranostics 8, 11 (2018)

    Article  Google Scholar 

  23. T. Chen, W. Wu, H. Xiao, Y. Chen, M. Chen, J. Li, Intelligent drug delivery system based on mesoporous silica nanoparticles coated with an ultra-pH-sensitive gatekeeper and poly(ethylene glycol). ACS Macro. Lett. 5, 1 (2016)

    Article  Google Scholar 

  24. S. Li, W. Wu, K. Xiu, F. Xu, Z. Li, J. Li, Doxorubicin loaded pH-responsive micelles capable of rapid intracellular drug release for potential tumor therapy. J. Biomed. Nanotechnol. 10(8), 1480–1489 (2014)

    Article  CAS  PubMed  Google Scholar 

  25. S. Li, Z. Zhao, W. Wu, C. Ding, J. Li, Dual pH-responsive micelles with both charge-conversional property and hydrophobic–hydrophilic transition for effective cellular uptake and intracellular drug release. Polym. Chem. 7, 12 (2016)

    CAS  Google Scholar 

  26. L. Luo, W. Wu, D. Sun, H.B. Dai, Y. Wang, Y. Zhong, J.X. Wang, A. Maruf, D. Nurhidayah, X.J. Zhang, Y. Wang, G.-X. Wang, Acid-activated melittin for targeted and safe antitumor therapy. Bioconjug. Chem. 29, 9 (2018)

    Article  Google Scholar 

  27. W. Wu, M. Chen, J. Wang, Q. Zhang, S. Li, Z. Lin, J. Li, Nanocarriers with dual pH-sensitivity for enhanced tumor cell uptake and rapid intracellular drug release. RSC Adv. 4, 58 (2014)

    Google Scholar 

  28. W. Wu, J. Wang, Z. Lin, X. Li, J. Li, Tumor-acidity activated surface charge-conversion of polymeric nanocarriers for enhanced cell adhesion and targeted drug release. Macromol. Rapid Commun. 35, 19 (2014)

    Article  Google Scholar 

  29. W. Wu, Q. Zhang, J. Wang, M. Chen, S. Li, Z. Lin, J. Li, Tumor-targeted aggregation of pH-sensitive nanocarriers for enhanced retention and rapid intracellular drug release. Polym. Chem. 5, 19 (2014)

    Article  Google Scholar 

  30. S. Mura, J. Nicolas, P. Couvreur, Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 12, 11 (2013)

    Article  Google Scholar 

  31. J. Kim, J. Lee, Y.M. Lee, S. Pramanick, S. Im, W.J. Kim, Andrographolide-loaded polymerized phenylboronic acid nanoconstruct for stimuli-responsive chemotherapy. J. Control. Release. 259, 203–211 (2017)

    Article  CAS  PubMed  Google Scholar 

  32. H. Song, C. Wang, H. Zhang, L. Yao, J. Zhang, R. Gao, X. Tang, T. Chong, W. Liu, Y. Tang, A high-loading drug delivery system based on magnetic nanomaterials modified by hyperbranched phenylboronic acid for tumor-targeting treatment with pH response. Coll. Surf B.: Biointerfaces. 182, 110375 (2019)

    Article  CAS  Google Scholar 

  33. G. Zheng, J. Zheng, L. Xiao, T. Shang, Y. Cai, Y. Li, Y. Xu, X. Chen, Y. Liu, B. Yang, Construction of a phenylboronic acid-functionalized nano-prodrug for pH-responsive emodin delivery and antibacterial activity. ACS Omega 6, 12 (2021)

    Article  Google Scholar 

  34. J. Yan, G. Springsteen, S. Deeter, B. Wang, The relationship among pKa, pH, and binding constants in the interactions between boronic acids and diols—it is not as simple as it appears. Tetrahedron 60, 49 (2004)

    Article  Google Scholar 

  35. P. Zhang, Q. Xu, X. Li, Y. Wang, pH-responsive polydopamine nanoparticles for photothermally promoted gene delivery. Mater. Sci. Eng.: C. 108, 110396 (2020)

    Article  CAS  Google Scholar 

  36. L. Zhu, Z. Song, S. Feng, H. Xu, S. Chen, R. Feng, Biotin-modified oligochitosan-F127 micelles for honokiol’s encapsulation. J. Nanopart. Res. 23, 5 (2021)

    Article  Google Scholar 

  37. R. Feng, W. Wang, L. Zhu, H. Xu, S. Chen, Z. Song, Phenylboronic acid-functionalized F127-oligochitosan conjugate micelles for doxorubicin encapsulation. J. Biomed. Mater. Res. Part B. : Appl. Biomater. 108(8), 3345–3355 (2020)

    Article  CAS  Google Scholar 

  38. S. Khoee, A. Kavand, A new procedure for preparation of polyethylene glycol-grafted magnetic iron oxide nanoparticles. J. Nanostruct. Chem. 4, 3 (2014)

    Article  Google Scholar 

  39. A.A. D’souza, R. Shegokar, Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications. Expert Opin. Drug Deliv. 13, 9 (2016)

    Article  Google Scholar 

  40. L.E. Scheeren, D.R. Nogueira, L.B. Macedo, M.P. Vinardell, M. Mitjans, M.R. Infante, C.M. Rolim, PEGylated and poloxamer-modified chitosan nanoparticles incorporating a lysine-based surfactant for pH-triggered doxorubicin release. Coll. Surf B. Biointerfaces. 138, 117–127 (2016)

    Article  CAS  Google Scholar 

  41. Y. Zhang, L. Tang, L. Sun, J. Bao, C. Song, L. Huang, K. Liu, Y. Tian, G. Tian, Z. Li, H. Sun, L. Mei, A novel paclitaxel-loaded poly(epsilon-caprolactone)/poloxamer 188 blend nanoparticle overcoming multidrug resistance for cancer treatment. Acta. Biomater. 6, 6 (2010)

    Article  Google Scholar 

  42. C. Deng, C. Xu, X. Zhang, J.U. Yao, Y. Zhang, B.O. Yu, R.J. Lee, C. Jiang, A novel paclitaxel-loaded polymeric micelle system with favorable biocompatibility and superior antitumor activity. Anticancer. Res. 38, 1 (2018)

    Google Scholar 

  43. Y. Javadzadeh, F. Ahadi, S. Davaran, G. Mohammadi, A. Sabzevari, K. Adibkia, Preparation and physicochemical characterization of naproxen-PLGA nanoparticles. Coll. Surf B. Biointerfaces. 81, 2 (2010)

    Article  Google Scholar 

  44. R. Savić, A. Eisenberg, D. Maysinger, Block copolymer micelles as delivery vehicles of hydrophobic drugs: Micelle–cell interactions. J. Drug. Target. 14, 6 (2006)

    Article  Google Scholar 

  45. H.T. Chen, M.F. Neerman, A.R. Parrish, E.E. Simanek, Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery. J. Am. Chem. Soc. 126, 32 (2004)

    Google Scholar 

  46. Y. Liu, S. Fu, L. Lin, Y. Cao, X. Xie, H. Yu, M. Chen, H. Li, Redox-sensitive pluronic F127-tocopherol micelles: synthesis, characterization, and cytotoxicity evaluation. Int. J. Nanomed. 12, 2635-2644 (2017)

    Article  CAS  Google Scholar 

  47. T. Ramasamy, Z.S. Haidar, T.H. Tran, J.Y. Choi, J.H. Jeong, B.S. Shin, H.G. Choi, C.S. Yong, J.O. Kim, Layer-by-layer assembly of liposomal nanoparticles with PEGylated polyelectrolytes enhances systemic delivery of multiple anticancer drugs. Acta. Biomater. 10, 12 (2014)

    Article  Google Scholar 

  48. S. Bhattacharjee, DLS and zeta potential—what they are and what they are not? J. Controll. Release.: Off. J. Controll. Release. Soc. 235, 337–351 (2016)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (31971301, 32171324), Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0149), and Fundamental Research Funds for Central Universities (2020CDJQY-A061, 2018CDHB1B08). In addition, some large instruments and equipment were provided by the Analysis and Testing Center of Chongqing University.

Author information

Author notes

  1. Jiyu Li and Li Zhu have contributed equally to this article.

Authors and Affiliations

  1. Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China

    Jiyu Li, Li Zhu, Shuai Wu, Guixue Wang, Yidan Chen & Wei Wu

Authors
  1. Jiyu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuai Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guixue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yidan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WW and JL did the conception and design of the work. LZ did the acquisition and analysis of the data. SW interpreted the data. JL and LZ drafted the manuscript. YC and GW substantively revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yidan Chen or Wei Wu.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 116 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Zhu, L., Wu, S. et al. MPEG-phenylboronic acid modified doxorubicin as the efficient pathological pH-responsive nanoplatform for potential anti-cancer delivery. Macromol. Res. 31, 181–191 (2023). https://doi.org/10.1007/s13233-022-00106-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-022-00106-5

Keywords

Search

Navigation