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Co-delivery of doxorubicin and paclitaxel with linear-dendritic block copolymer for enhanced anti-cancer efficacy

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  • Special Issue Recent Research Progress of Biomedical Polymers
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Abstract

A series of well-defined amphiphilic linear-dendritic block copolymers (telodendrimers, MPEG-b-PAMAM-cholesterol) with 1,2,4 or 8 cholesteryl groups (named as P1, P2, P4, P8, respectively) were synthesized. Their chemical structures were characterized with 1H NMR and mass spectrum (MALDI-TOF MS). The telodendrimers could self-assemble into micelles in aqueous solution, and encapsulate chemotherapeutic drug doxorubicin (DOX) and paclitaxel (PTX) for combination therapy. All the telodendrimers could encapsulate DOX with similar capability. However, their drug-loading capability of PTX is increased with the increasing number of cholesteryl groups. P8 exhibited much higher PTX loading efficiency than its counterparts. Thus, P8 was selected for further application of drug delivery in the paper. The drug-loading micellar nanoparticles (NPs) of P8 were spherical in shape and their diameters were less than 150 nm which were determined by dynamic light scattering measurements (DLS) and transmission electron microscope (TEM). In vitro drug release experiment demonstrated that P8 exhibited a controlled release manner for both DOX and PTX, and the two drugs were released simultaneously. In vitro cytotoxicity experiment further demonstrated that the co-delivery of DOX and PTX in P8 exhibited better anti-cancer efficiency than the delivery systems encapsulated with single drug (DOX or PTX). This indicates a synergistic effect. The co-delivery system showed potential in future anti-cancer treatment.

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References

  1. Amass W, Amass A, Tighe B. A review of biodegradable polymers: uses, current developments in the synthesis and characterization of biodegradable polyesters, blends of biodegradable polymers and recent advances in biodegradation studies. Polym Int, 1998, 47: 89–144

    Article  CAS  Google Scholar 

  2. Oh JK, Drumright R, Siegwart, DJ, Matyjaszewski K. The development of microgels/nanogels for drug delivery applications. Prog Polym Sci, 2008, 33: 448–477

    Article  CAS  Google Scholar 

  3. Deng J, Yu DH, Gao CY. Biological identity of nanomaterials: opportunities and challenges. Sci China Chem, 2013, 56: 1533–1541

    Article  CAS  Google Scholar 

  4. Torchilin VP. Micellar nanocarriers: pharmaceutical perspectives. Pharm Res, 2007, 24: 1–16

    Article  CAS  Google Scholar 

  5. Zheng X, Jiang, T, He F. Synthesis and characterization of pnipam-b-polycarbonate copolymers as self-assembled thermosensitive micelles for drug delivery. Acta Polym Sin, 2011, 8: 895–902

    Article  Google Scholar 

  6. Yu SF, Wang Z, Wu GL, Wang YN, Gao H, Ma JB. Anti-tumor drug delivery of a pH-sensitive poly(aspartic acid)-containing block copolymer. Acta Polym Sin, 2012, 4: 427–432

    Article  Google Scholar 

  7. Bu H, Gao Y, Li Y. Overcoming multidrug resistance (MDR) in cancer by nanotechnology. Sci China Chem, 2010, 53: 2226–2232

    Article  CAS  Google Scholar 

  8. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul, 2001, 41: 189–207

    Article  CAS  Google Scholar 

  9. Brigger I, Dubernet C, Convreur P, Nanoparticles in cancer therapy and diagnosis. Adv Drug Delivery Rev, 2002, 54: 631–651

    Article  CAS  Google Scholar 

  10. Yue J, Wang R, Liu S, Wu S, Xie ZG, Huang YB, Jing XB. Reduction-responsive shell-crosslinked micelles prepared from Y-shaped amphiphilic block copolymers as a drug carrier. Soft Matter, 2012, 8: 7426–7435

    Article  CAS  Google Scholar 

  11. Wurm F, Frey H, Linear-dendritic block copolymers: the state of the art and exciting perspectives. Prog Polym Sci, 2011, 36: 1–52

    Article  CAS  Google Scholar 

  12. Xu YC, Dong CM. Dendron-like poly(ɛ-benzyloxycarbonyl-l-lysine)/linear PEO block copolymers: synthesis, physical characterization, self-assembly, and drug-release behavior. J Polym Sci, Part A: Polym Chem, 2012, 50: 1216–1225

    Article  CAS  Google Scholar 

  13. Sousa-Herves A, Riguera R, Fernandez-Megia E. PEG-dendritic block copolymers for biomedical applications. New J Chem, 2012, 36: 205–210

    Article  CAS  Google Scholar 

  14. Luo J, Xiao K, Li Y, Lee JS, Shi L, Tan YH, Xing L, Cheng RH, Liu GY, Lam KS. Well-defined, size-tunable, multifunctional micelles for efficient paclitaxel delivery for cancer treatment. Bioconjugate Chem, 2010, 21: 1216–1224

    Article  CAS  Google Scholar 

  15. Xiao K, Li Y, Luo J, Lee JS, Xiao W, Gonik AM, Agarwal RG, Lam KS. The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles. Biomaterials, 2011, 32: 3435–3446

    Article  CAS  Google Scholar 

  16. Zhu C, Jung S, Luo S, Meng F, Zhu X, Park TG, Zhong Z. Co-delivery of siRNA and paclitaxel into cancer cells by biodegra-dable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers. Biomaterials, 2010, 31: 2408–2416

    Article  CAS  Google Scholar 

  17. Mishra GP, Nguyen D, Alani AW. Inhibitory effect of paclitaxel and rapamycin individual and dual drug-loaded polymeric micelles in the angiogenic cascade. Mol Pharm, 2013, 10: 2071–2078

    Article  CAS  Google Scholar 

  18. Wang H, Zhao Y, Wu Y, Hu YL, Nan K, Nie G, Chen H. Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials, 2011, 32: 8281–8290

    Article  CAS  Google Scholar 

  19. Ahmed F, Pakunlu RI, Brannan A, Bates F, Minko T, Discher DE. Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. J Controlled Release, 2006, 116: 150–158

    Article  CAS  Google Scholar 

  20. Li M, Song W, Tang Z, Lv S, Lin L, Sun H, Li Q, Yang Y, Hong H, Chen X. Nanoscaled poly(L-glutamic acid)/doxorubicin-amphiphile complex as pH-responsive drug delivery system for effective treatment of nonsmall cell lung cancer. Acs Appl Mater Interfaces, 2013, 5: 1781–1792

    Article  CAS  Google Scholar 

  21. Zhang Y, Xiao C, Li M, Chen J, Ding J, He C, Zhuang X, Chen X. Co-delivery of 10-hydroxycamptothecin with doxorubicin conjugated prodrugs for enhanced anticancer efficacy. Macromol Biosci, 2013, 13: 584–594

    Article  CAS  Google Scholar 

  22. Li D, Ding JX, Tang ZH, Sun H, Zhuang XL, Xu JZ, Chen XS. In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers. Int J Nanomed, 2012, 7, 2687–2697

    CAS  Google Scholar 

  23. He H, Li Y, Jia XR, Du J, Ying X, Lu WL, Lou JN, Wei Y. PEGylated poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials, 2011, 32: 478–487

    Article  CAS  Google Scholar 

  24. Dan L, Kraig H, Nadya B, Ernest H, Saltzman WM. Poly(ethylene glycol)-conjugated PAMAM dendrimer for biocompatible, high-efficiency DNA delivery. Macromolecules, 2002, 35: 3456–3462

    Article  CAS  Google Scholar 

  25. Guan X, Li Y, Jiao Z, Chen J, Guo Z, Tian H, Chen X. A pH-sensitive charge-conversion system for doxorubicin delivery. Acta Biomater, 2013, 9: 7672–7678

    Article  CAS  Google Scholar 

  26. Ding J, Shi F, Xiao C, Lin L, Chen L, He C, Zhuang X, Chen X. One-step preparation of reduction-responsive poly(ethylene glycol)-poly(amino acid)s nanogels as efficient intracellular drug delivery platforms. Polym Chem, 2011, 2: 2857–2864

    Article  CAS  Google Scholar 

  27. Maruyama K. Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Delivery Rev, 2011, 63: 161–169

    Article  CAS  Google Scholar 

  28. Xiao C, Tian H, Zhuang X, Chen X, Jing X. Recent developments in intelligent biomedical polymers. Sci China Chem, 2009, 52: 117–130

    Article  CAS  Google Scholar 

  29. Lee ALZ, Venkataraman S, Sirat SBM, Gao S, Hedrick JL, Yang YY. The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs. Biomaterials, 2012, 33: 1921–1928

    Article  CAS  Google Scholar 

  30. Lee SM, O’Halloran TV, Nguyen ST. Polymer-caged nanobins for synergistic cisplatin-doxorubicin combination chemotherapy. J Am Chem Soc, 2010, 132: 17130–17138

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Key Laboratory of Polymer Ecomaterials, Chanchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Yu Zhang, ChunSheng Xiao, MingQiang Li, JianXun Ding, ChenGuang Yang, XiuLi Zhuang & XueSi Chen

  2. University of Chinese Academy of Sciences, Beijing, 100039, China

    Yu Zhang & MingQiang Li

Authors
  1. Yu Zhang
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  2. ChunSheng Xiao
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  3. MingQiang Li
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  4. JianXun Ding
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  5. ChenGuang Yang
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  6. XiuLi Zhuang
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  7. XueSi Chen
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Correspondence to XueSi Chen.

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Zhang, Y., Xiao, C., Li, M. et al. Co-delivery of doxorubicin and paclitaxel with linear-dendritic block copolymer for enhanced anti-cancer efficacy. Sci. China Chem. 57, 624–632 (2014). https://doi.org/10.1007/s11426-014-5078-y

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  • DOI: https://doi.org/10.1007/s11426-014-5078-y

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