Advertisement

Synthesis of poly(ethylene glycol)-SS-poly(ε-caprolactone)-SS-poly(ethylene glycol) triblock copolymers via end-group conjugation and self-assembly for reductively responsive drug delivery

  • Junbo LiEmail author
  • Junting Jiang
  • Biyu Zhou
  • Chaohuang Niu
  • Wendi Wang
  • Wenlan Wu
Research Article
  • 4 Downloads

Abstract

In this study, we describe a simple synthesis route to prepare triblock copolymers with disulfide-linkers, poly(ethylene glycol)-SS-poly(ε-caprolactone)-SS-poly (ethylene glycol) (PEG-SS-PCL-SS-PEG) for application in the reductively responsive release of doxorubicin (DOX). To synthesize PEG-SS-PCL-SS-PEG, two end-groups of PCL-diol were first modified with cystamine to introduce disulfide bonds and subsequently conjugated with PEG-NHS via carbodiimide chemistry. PEG-SS-PCL-SSPEG fabricated into polymeric micelles with stable structure and different nanoscale sizes via adjusting the PCL chain length, showing obvious reductive responsiveness and fast drug release of encapsulated DOX in the presence of glutathione (GSH). Moreover, DOX-loaded PEG-SS-PCL-SS-PEG micelles exhibited higher therapeutic efficacy than reduction-insensitive PEG-b-PCL micelles in vitro. Thus, end-groups conjugation is a simple and straightforward strategy to introduce intelligent responsiveness in biocompatible block copolymers and improve their therapeutic efficacy.

Keywords

poly-ε-caprolactone poly(ethylene glycol) block copolymer reductive responsiveness drug release 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Project U1704150) and the Scientific and Technological Projects of Henan Province (182102410017).

References

  1. [1]
    Popat S, O’Brien M. Chemotherapy strategies in the treatment of small cell lung cancer. Anti-Cancer Drugs, 2005, 16(4): 361–372CrossRefGoogle Scholar
  2. [2]
    Liu D, Poon C, Lu K, et al. Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy. Nature Communications, 2014, 5(1): 4182CrossRefGoogle Scholar
  3. [3]
    Poon C, He C, Liu D, et al. Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer. Journal of Controlled Release, 2015, 201: 90–99CrossRefGoogle Scholar
  4. [4]
    He C, Liu D, Lin W. Self-assembled nanoscale coordination polymers carrying siRNAs and cisplatin for effective treatment of resistant ovarian cancer. Biomaterials, 2015, 36: 124–133CrossRefGoogle Scholar
  5. [5]
    He C, Liu D, Lin W. Self-assembled core–shell nanoparticles for combined chemotherapy and photodynamic therapy of resistant head and neck cancers. ACS Nano, 2015, 9(1): 991–1003CrossRefGoogle Scholar
  6. [6]
    He C, Poon C, Chan C, et al. Nanoscale coordination polymers codeliver chemotherapeutics and siRNAs to eradicate tumors of cisplatin-resistant ovarian cancer. Journal of the American Chemical Society, 2016, 138(18): 6010–6019CrossRefGoogle Scholar
  7. [7]
    Li X, Yang Z, Yang K, et al. Self-assembled polymeric micellar nanoparticles as nanocarriers for poorly soluble anticancer drug ethaselen. Nanoscale Research Letters, 2009, 4(12): 1502–1511CrossRefGoogle Scholar
  8. [8]
    Xiong D, Yao N, Gu H, et al. Stimuli-responsive shell cross-linked micelles from amphiphilic four-arm star copolymers as potential nanocarriers for “pH/redox-triggered” anticancer drug release. Polymer, 2017, 114: 161–172CrossRefGoogle Scholar
  9. [9]
    Cabral H, Kataoka K. Progress of drug-loaded polymeric micelles into clinical studies. Journal of Controlled Release, 2014, 190: 465–476CrossRefGoogle Scholar
  10. [10]
    Kwon G S, Kataoka K. Block copolymer micelles as longcirculating drug vehicles. Advanced Drug Delivery Reviews, 2012, 64: 237–245CrossRefGoogle Scholar
  11. [11]
    Deng C, Jiang Y, Cheng R, et al. Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: Promises, progress and prospects. Nano Today, 2012, 7(5): 467–480CrossRefGoogle Scholar
  12. [12]
    Cao Z, Ma Y, Sun C, et al. ROS-sensitive polymeric nanocarriers with red light-activated size shrinkage for remotely controlled drug release. Chemistry of Materials, 2017, 30: 517–515CrossRefGoogle Scholar
  13. [13]
    Adams M L, Lavasanifar A, Kwon G S. Amphiphilic block copolymers for drug delivery. Journal of Pharmaceutical Sciences, 2003, 92(7): 1343–1355CrossRefGoogle Scholar
  14. [14]
    Cao Z, Yu Q, Xue H, et al. Nanoparticles for drug delivery prepared from amphiphilic PLGA zwitterionic block copolymers with sharp contrast in polarity between two blocks. Angewandte Chemie International Edition, 2010, 49(22): 3771–3776CrossRefGoogle Scholar
  15. [15]
    Zhu X, Fryd M, Wayland B B. Kinetic-mechanistic studies of lipase-polymer micelle binding and catalytic degradation: Enzyme interfacial activation. Polymer Degradation and Stability, 2013, 98(6): 1173–1181CrossRefGoogle Scholar
  16. [16]
    Zhao L, Wu C, Wang F, et al. Fabrication of biofunctional complex micelles with tunable structure for application in controlled drug release. Colloid & Polymer Science, 2014, 292(7): 1675–1683CrossRefGoogle Scholar
  17. [17]
    Deng H, Liu J, Zhao X, et al. PEG-b-PCL copolymer micelles with the ability of pH-controlled negative-to-positive charge reversal for intracellular delivery of doxorubicin. Biomacromolecules, 2014, 15(11): 4281–4292CrossRefGoogle Scholar
  18. [18]
    Marzbali M Y, Khosroushahi A Y. Polymeric micelles as mighty nanocarriers for cancer gene therapy: a review. Cancer Chemotherapy and Pharmacology, 2017, 79(4): 637–649CrossRefGoogle Scholar
  19. [19]
    Choi J Y, Thapa R K, Yong C S, et al. Nanoparticle-based combination drug delivery systems for synergistic cancer treatment. Journal of Pharmaceutical Investigation, 2016, 46(4): 325–339CrossRefGoogle Scholar
  20. [20]
    Senapati S, Mahanta A K, Kumar S, et al. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduction and Targeted Therapy, 2018, 3(1): 7CrossRefGoogle Scholar
  21. [21]
    Hu Y W, Du Y Z, Liu N, et al. Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier. Journal of Controlled Release, 2015, 206: 91–100CrossRefGoogle Scholar
  22. [22]
    Sun H, Guo B, Li X, et al. Shell-sheddable micelles based on dextran-SS-poly(ε-caprolactone) diblock copolymer for efficient intracellular release of doxorubicin. Biomacromolecules, 2010, 11(4): 848–854CrossRefGoogle Scholar
  23. [23]
    Sun H, Guo B, Cheng R, et al. Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials, 2009, 30(31): 6358–6366CrossRefGoogle Scholar
  24. [24]
    Zhong Y, Yang W, Sun H, et al. Ligand-directed reductionsensitive shell-sheddable biodegradable micelles actively deliver doxorubicin into the nuclei of target cancer cells. Biomacromolecules, 2013, 14(10): 3723–3730CrossRefGoogle Scholar
  25. [25]
    Zhao C, Shao L, Lu J, et al. Triple redox responsive poly(ethylene glycol)-polycaprolactone polymeric nanocarriers for fine-controlled drug release. Macromolecular Bioscience, 2017, 17(4): 1600295CrossRefGoogle Scholar
  26. [26]
    Tao Y, Zhao H. Synthesis and self-assembly of amphiphilic tadpole-shaped block copolymer with disulfides at the junction points between cyclic PEG and linear PS. Polymer, 2017, 122: 52–59CrossRefGoogle Scholar
  27. [27]
    Kumar A, Lale S V, Mahajan S, et al. ROP and ATRP fabricated dual targeted redox sensitive polymersomes based on pPEGMAPCL-ss-PCL-pPEGMA triblock copolymers for breast cancer therapeutics. ACS Applied Materials & Interfaces, 2015, 7(17): 9211–9227CrossRefGoogle Scholar
  28. [28]
    Fan X, Wang X, Cao M, et al. “Y”-shape armed amphiphilic starlike copolymers: design, synthesis and dual-responsive unimolecular micelle formation for controlled drug delivery. Polymer Chemistry, 2017, 8(36): 5611CrossRefGoogle Scholar
  29. [29]
    Jiang J, Li J, Zhou B, et al. Fabrication of polymer micelles with Zwitterionic shell and biodegradable core for reductively responsive release of doxorubicin. Polymers, 2019, 11(6): 1019CrossRefGoogle Scholar
  30. [30]
    Yan T, Li D, Li J, et al. Effective co-delivery of doxorubicin and curcumin using a glycyrrhetinic acid-modified chitosancystamine-poly(ε-caprolactone) copolymer micelle for combination cancer chemotherapy. Colloids and Surfaces B: Biointerfaces, 2016, 145: 526–538CrossRefGoogle Scholar
  31. [31]
    Davoodi P, Srinivasan M P, Wang C H. Synthesis of intracellular reduction-sensitive amphiphilic polyethyleneimine and poly(ε-caprolactone) graft copolymer for on-demand release of doxorubicin and p53 plasmid DNA. Acta Biomaterialia, 2016, 39: 79–93CrossRefGoogle Scholar
  32. [32]
    Torchilin V P. Structure and design of polymeric surfactant-based drug delivery systems. Journal of Controlled Release, 2001, 73(2–3): 137–172CrossRefGoogle Scholar
  33. [33]
    Xu Y, Wang L, Li Y K, et al. Reduction and pH dual-responsive nanoparticles based chitooligosaccharide-based graft copolymer for doxorubicin delivery. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2016, 497: 8–15CrossRefGoogle Scholar
  34. [34]
    Chen Y, Zhang W, Huang Y, et al. In vivo biodistribution and antitumor efficacy evaluation of doxorubicin and paclitaxel-loaded pluronic micelles decorated with c(RGDyK) peptide. PLoS One, 2016, 11(3): e0149952CrossRefGoogle Scholar
  35. [35]
    Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nature Materials, 2013, 12(11): 991–1003CrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Junbo Li
    • 1
    Email author
  • Junting Jiang
    • 1
  • Biyu Zhou
    • 1
  • Chaohuang Niu
    • 1
  • Wendi Wang
    • 1
  • Wenlan Wu
    • 2
  1. 1.School of Chemical Engineering and PharmaceuticsHenan University of Science and TechnologyLuoyangChina
  2. 2.School of MedicineHenan University of Science and TechnologyLuoyangChina

Personalised recommendations