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Synthesis strategies for disulfide bond-containing polymer-based drug delivery system for reduction-responsive controlled release

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Abstract

Tumor micro-environment responsive drug delivery systems (DDSs) have been developed as a potential approach to reduce the side effects of cancer chemotherapy. Glutathione (GSH) has been supposed to the most significant signal of the difference between the normal tissue and the tumor cells, besides the media pH and temperature. In recent years, the reduction-responsive DDSs have attracted more and more attention for delivery of anti-cancer drugs, based on such physiological signal. Among them, disulfide bond-containing polymers have been designed as the main tool for the purpose. The recent progress in the synthesis strategies for the disulfide bond-containing polymer-based DDS is focused in the present review.

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References

  1. Peer D, Karp J M, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2007, 2(12): 751–760

    Article  Google Scholar 

  2. Barreto J A, O’Malley W, Kubeil M, et al. Nanomaterials: applications in cancer imaging and therapy. Advanced Materials, 2011, 23(12): H18–H40

    Article  Google Scholar 

  3. Maeda H, Wu J, Sawa T, et al. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of Controlled Release, 2000, 65(1–2): 271–284

    Article  Google Scholar 

  4. Huo M, Yuan J, Tao L, et al. Redox-responsive polymers for drug delivery: from molecular design to applications. Polymer Chemistry, 2014, 5(5): 1519–1528

    Article  Google Scholar 

  5. Yin Q, Shen J, Zhang Z, et al. Reversal of multidrug resistance by stimuli-responsive drug delivery systems for therapy of tumor. Advanced Drug Delivery Reviews, 2013, 65(13–14): 1699–1715

    Article  Google Scholar 

  6. Chan A, Orme R P, Fricker R A, et al. Remote and local control of stimuli responsive materials for therapeutic applications. Advanced Drug Delivery Reviews, 2013, 65(4): 497–514

    Article  Google Scholar 

  7. Ganta S, Devalapally H, Shahiwala A, et al. A review of stimuli-responsive nanocarriers for drug and gene delivery. Journal of Controlled Release, 2008, 126(3): 187–204

    Article  Google Scholar 

  8. Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Research, 1989, 49(23): 6449–6465

    Google Scholar 

  9. Hunt C A, Macgregor R D, Siegel R A. Engineering targeted in vivo drug delivery. I. The physiological and physicochemical principles governing opportunities and limitations. Pharmaceutical Research, 1986, 3(6): 333–344

    Article  Google Scholar 

  10. Du J Z, Du X J, Mao C Q, et al. Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. Journal of the American Chemical Society, 2011, 133(44): 17560–17563

    Article  Google Scholar 

  11. Fan L, Wu H, Zhang H, et al. Novel super pH-sensitive nanoparticles responsive to tumor extracellular pH. Carbohydrate Polymers, 2008, 73(3): 390–400

    Article  Google Scholar 

  12. Ding H, Wu F, Huang Y, et al. Synthesis and characterization of temperature-responsive copolymer of PELGA modified poly(N-isopropylacrylamide). Polymer, 2006, 47(5): 1575–1583

    Article  Google Scholar 

  13. Chen W, Zhong P, Meng F, et al. Redox and pH-responsive degradable micelles for dually activated intracellular anticancer drug release. Journal of Controlled Release, 2013, 169(3): 171–179

    Article  Google Scholar 

  14. Wu G, Fang Y Z, Yang S, et al. Glutathione metabolism and its implications for health. The Journal of Nutrition, 2004, 134(3): 489–492

    Google Scholar 

  15. Schafer F Q, Buettner G R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology & Medicine, 2001, 30(11): 1191–1212

    Article  Google Scholar 

  16. Cheng R, Meng F, Deng C, et al. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials, 2013, 34(14): 3647–3657

    Article  Google Scholar 

  17. Cheng R, Feng F, Meng F, et al. Glutathione-responsive nanovehicles as a promising platform for targeted intracellular drug and gene delivery. Journal of Controlled Release, 2011, 152(1): 2–12

    Article  Google Scholar 

  18. Phillips D J, Gibson M I. Redox-sensitive materials for drug delivery: targeting the correct intracellular environment, tuning release rates, and appropriate predictive systems. Antioxidants & Redox Signaling, 2014, 21(5): 786–803

    Article  Google Scholar 

  19. Huo M, Yuan J Y, Tao L, et al. Redox-responsive polymers for drug delivery: from molecular design to applications. Polymer Chemistry, 2014, 5(5): 1519–1528

    Article  Google Scholar 

  20. Deng C, Jiang Y J, Cheng R, et al. Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: Promises, progress and prospects. Nano Today, 2012, 7(5): 467–480

    Article  Google Scholar 

  21. Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Advanced drug delivery reviews, 2001, 47(1): 113–131

    Article  Google Scholar 

  22. Ahmad Z, Shah A, Siddiq M, et al. Polymeric micelles as drug delivery vehicles. RSC Advances, 2014, 4(33): 17028–17038

    Article  Google Scholar 

  23. Cabral H, Kataoka K. Progress of drug-loaded polymeric micelles into clinical studies. Journal of Controlled Release, 2014, 190: 465–476

    Article  Google Scholar 

  24. van Vlerken L E, Vyas T K, Amiji M M. Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharmaceutical Research, 2007, 24(8): 1405–1414

    Article  Google Scholar 

  25. Knop K, Hoogenboom R, Fischer D, et al. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angewandte Chemie International Edition, 2010, 49(36): 6288–6308

    Article  Google Scholar 

  26. Li Y, Xiao K, Zhu W, et al. Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers. Advanced Drug Delivery Reviews, 2014, 66: 58–73

    Article  Google Scholar 

  27. Wei H, Zhuo R X, Zhang X Z. Design and development of polymeric micelles with cleavable links for intracellular drug delivery. Progress in Polymer Science, 2013, 38(3–4): 503–535

    Article  Google Scholar 

  28. Cheng R, Feng F, Meng F, et al. Glutathione-responsive nanovehicles as a promising platform for targeted intracellular drug and gene delivery. Journal of Controlled Release, 2011, 152(1): 2–12

    Article  Google Scholar 

  29. Wang Y C, Wang F, Sun T M, et al. Redox-responsive nanoparticles from the single disulfide bond-bridged block copolymer as drug carriers for overcoming multidrug resistance in cancer cells. Bioconjugate Chemistry, 2011, 22(10): 1939–1945

    Article  Google Scholar 

  30. Ding J, Chen J, Li D, et al. Biocompatible reduction-responsive polypeptide micelles as nanocarriers for enhanced chemotherapy efficacy in vitro. Journal of Materials Chemistry B, 2013, 1(1): 69–81

    Article  Google Scholar 

  31. Xu P, Yu H, Zhang Z, et al. Hydrogen-bonded and reduction-responsive micelles loading atorvastatin for therapy of breast cancer metastasis. Biomaterials, 2014, 35(26): 7574–7587

    Article  Google Scholar 

  32. Sun H, Guo B, Li X, et al. Shell-sheddable micelles based on dextran-SS-poly(ɛ-caprolactone) diblock copolymer for efficient intracellular release of doxorubicin. Biomacromolecules, 2010, 11(4): 848–854

    Article  Google Scholar 

  33. Thambi T, Deepagan V G, Ko H, et al. Bioreducible polymersomes for intracellular dual-drug delivery. Journal of Materials Chemistry, 2012, 22(41): 22028–22036

    Article  Google Scholar 

  34. Cunningham A, Ko N R, Oh J K. Synthesis and reduction-responsive disassembly of PLA-based mono-cleavable micelles. Colloids and Surfaces B: Biointerfaces, 2014, 122: 693–700

    Article  Google Scholar 

  35. Wang X, Sun H, Meng F, et al. Galactose-decorated reduction-sensitive degradable chimaeric polymersomes as a multifunctional nanocarrier to efficiently chaperone apoptotic proteins into hepatoma cells. Biomacromolecules, 2013, 14(8): 2873–2882

    Article  Google Scholar 

  36. Yuan W, Zou H, Guo W, et al. Supramolecular micelles with dual temperature and redox responses for multi-controlled drug release. Polymer Chemistry, 2013, 4(9): 2658–2661

    Article  Google Scholar 

  37. Li Y, Tong R, Xia H, et al. High intensity focused ultrasound and redox dual responsive polymer micelles. Chemical Communications, 2010, 46(41): 7739–7741

    Article  Google Scholar 

  38. Klaikherd A, Nagamani C, Thayumanavan S. Multi-stimuli sensitive amphiphilic block copolymer assemblies. Journal of the American Chemical Society, 2009, 131(13): 4830–4838

    Article  Google Scholar 

  39. Han D, Tong X, Zhao Y. Block copolymer micelles with a dualstimuli-responsive core for fast or slow degradation. Langmuir, 2012, 28(5): 2327–2331

    Article  Google Scholar 

  40. Guo X, Shi C, Yang G, et al. Dual-responsive polymer micelles for target-cell-specific anticancer drug delivery. Chemistry of Materials, 2014, 26(15): 4405–4418

    Article  Google Scholar 

  41. Yu C, Gao C, Lü S, et al. Redox-responsive shell-sheddable micelles self-assembled from amphiphilic chondroitin sulfate-cholesterol conjugates for triggered intracellular drug release. Chemical Engineering Journal, 2013, 228: 290–299

    Article  Google Scholar 

  42. Li S, Ye C, Zhao G, et al. Synthesis and properties of monocleavable amphiphilic comblike copolymers with alternating PEG and PCL grafts. Journal of Polymer Science Part A: Polymer Chemistry, 2012, 50(15): 3135–3148

    Article  Google Scholar 

  43. Aleksanian S, Khorsand B, Schmidt R, et al. Rapidly thiolresponsive degradable block copolymer nanocarriers with facile bioconjugation. Polymer Chemistry, 2012, 3(8): 2138–2147

    Article  Google Scholar 

  44. Ko N R, Oh J K. Glutathione-triggered disassembly of dual disulfide located degradable nanocarriers of polylactide-based block copolymers for rapid drug release. Biomacromolecules, 2014, 15(8): 3180–3189

    Article  Google Scholar 

  45. Liu X, He J, Hu D, et al. Facile synthesis of a reduction-responsive amphiphilic triblock polymer via a selective thiol-disulfide exchange reaction. RSC Advances, 2014, 4(90): 48897–48900

    Article  Google Scholar 

  46. Wu Y, Kuang H, Xie Z, et al. Novel hydroxyl-containing reduction-responsive pseudo-poly (aminoacid) via click polymerization as an efficient drug carrier. Polymer Chemistry, 2014, 5(15): 4488–4498

    Article  Google Scholar 

  47. Wang S, Zhang S, Liu J, et al. pH- and reduction-responsive polymeric lipid vesicles for enhanced tumor cellular internalization and triggered drug release. ACS Applied Materials & Interfaces, 2014, 6(13): 10706–10713

    Article  Google Scholar 

  48. Zhang S, Zhao Y. Rapid release of entrapped contents from multifunctionalizable, surface cross-linked micelles upon different stimulation. Journal of the American Chemical Society, 2010, 132(31): 10642–10644

    Article  Google Scholar 

  49. van Nostrum C F. Covalently cross-linked amphiphilic block copolymer micelles. Soft Matter, 2011, 7(7): 3246–3259

    Article  Google Scholar 

  50. Yue J, Wang R, Liu S, et al. Reduction-responsive shell-crosslinked micelles prepared from Y-shaped amphiphilic block copolymers as a drug carrier. Soft Matter, 2012, 8(28): 7426–7435

    Article  Google Scholar 

  51. Thambi T, Deepagan V G, Ko H, et al. Biostable and bioreducible polymersomes for intracellular delivery of doxorubicin. Polymer Chemistry, 2014, 5(16): 4627–4634

    Article  Google Scholar 

  52. Huang P, Liu J, Wang W, et al. Zwitterionic nanoparticles constructed with well-defined reduction-responsive shell and pH-sensitive core for “spatiotemporally pinpointed” drug delivery. ACS Applied Materials & Interfaces, 2014, 6(16): 14631–14643

    Article  Google Scholar 

  53. Zhao X, Liu P. Reduction-responsive core-shell-corona micelles based on triblock copolymers: novel synthetic strategy, characterization, and application as a tumor microenvironment-responsive drug delivery system. ACS Applied Materials & Interfaces, 2015, 7(1): 166–174

    Article  Google Scholar 

  54. Kommareddy S, Amiji M. Poly(ethylene glycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery. Nanomedicine: Nanotechnology, Biology, and Medicine, 2007, 3(1): 32–42

    Article  Google Scholar 

  55. Li Y L, Zhu L, Liu Z, et al. Reversibly stabilized multifunctional dextran nanoparticles efficiently deliver doxorubicin into the nuclei of cancer cells. Angewandte Chemie International Edition, 2009, 48(52): 9914–9918

    Article  Google Scholar 

  56. Zhang A, Zhang Z, Shi F, et al. Disulfide crosslinked PEGylated starch micelles as efficient intracellular drug delivery platforms. Soft Matter, 2013, 9(7): 2224–2233

    Article  Google Scholar 

  57. Ryu J H, Chacko R T, Jiwpanich S, et al. Self-cross-linked polymer nanogels: a versatile nanoscopic drug delivery platform. Journal of the American Chemical Society, 2010, 132(48): 17227–17235

    Article  Google Scholar 

  58. Cheng Y, He C, Xiao C, et al. Reduction-responsive cross-linked micelles based on PEGylated polypeptides prepared via click chemistry. Polymer Chemistry, 2013, 4(13): 3851–3858

    Article  Google Scholar 

  59. Zhang Q, Aleksanian S, Noh S M, et al. Thiol-responsive block copolymer nanocarriers exhibiting tunable release with morphology changes. Polymer Chemistry, 2013, 4(2): 351–359

    Article  Google Scholar 

  60. Wei R, Cheng L, Zheng M, et al. Reduction-responsive disassemblable core-cross-linked micelles based on poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide)-lipoic acid conjugates for triggered intracellular anticancer drug release. Biomacromolecules, 2012, 13(8): 2429–2438

    Article  Google Scholar 

  61. Li L H, Jiang X L, Zhuo R X. Synthesis and characterization of thermoresponsive polymers containing reduction-sensitive disulfide linkage. Journal of Polymer Science Part A: Polymer Chemistry, 2009, 47(22): 5989–5997

    Article  Google Scholar 

  62. Sun R, Luo Q, Gao C, et al. Facile fabrication of reduction-responsive nanocarriers for controlled drug release. Polymer Chemistry, 2014, 5(17): 4879–4883

    Article  Google Scholar 

  63. Li M, Tang Z, Sun H, et al. pH and reduction dual-responsive nanogel cross-linked by quaternization reaction for enhanced cellular internalization and intracellular drug delivery. Polymer Chemistry, 2013, 4(4): 1199–1207

    Article  Google Scholar 

  64. Chan N, Yee N, An S Y, et al. Tuning amphiphilicity/temperature-induced self-assembly and in-situ disulfide crosslinking of reduction-responsive block copolymers. Journal of Polymer Science Part A: Polymer Chemistry, 2014, 52(14): 2057–2067

    Article  Google Scholar 

  65. Jia Z, Liu J, Boyer C, et al. Functional disulfide-stabilized polymer-protein particles. Biomacromolecules, 2009, 10(12): 3253–3258

    Article  Google Scholar 

  66. Ding J, Shi F, Xiao C, et al. One-step preparation of reduction-responsive poly (ethylene glycol)-poly (amino acid)s nanogels as efficient intracellular drug delivery platforms. Polymer Chemistry, 2011, 2(12): 2857–2864

    Article  Google Scholar 

  67. Ulasan M, Yavuz E, Bagriacik E U, et al. Biocompatible thermoresponsive PEGMA nanoparticles crosslinked with cleavable disulfide-based crosslinker for dual drug release. Journal of Biomedical Materials Research Part A, 2015, 103(1): 243–251

    Article  Google Scholar 

  68. Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Advanced Materials, 2012, 24(12): 1504–1534

    Article  Google Scholar 

  69. Liu R, Zhao X, Wu T, et al. Tunable redox-responsive hybrid nanogated ensembles. Journal of the American Chemical Society, 2008, 130(44): 14418–14419

    Article  Google Scholar 

  70. Liu R, Zhang Y, Feng P. Multiresponsive supramolecular nanogated ensembles. Journal of the American Chemical Society, 2009, 131(42): 15128–15129

    Article  Google Scholar 

  71. Mortera R, Vivero-Escoto J, Slowing I I, et al. Cell-induced intracellular controlled release of membrane impermeable cysteine from a mesoporous silica nanoparticle-based drug delivery system. Chemical Communications, 2009, (22): 3219–3221

    Google Scholar 

  72. Sauer A M, Schlossbauer A, Ruthardt N, et al. Role of endosomal escape for disulfide-based drug delivery from colloidal mesoporous silica evaluated by live-cell imaging. Nano Letters, 2010, 10(9): 3684–3691

    Article  Google Scholar 

  73. Zhao Q, Geng H, Wang Y, et al. Hyaluronic acid oligosaccharide modified redox-responsive mesoporous silica nanoparticles for targeted drug delivery. ACS Applied Materials & Interfaces, 2014, 6(22): 20290–20299

    Article  Google Scholar 

  74. Luo Z, Cai K, Hu Y, et al. Mesoporous silica nanoparticles endcapped with collagen: redox-responsive nanoreservoirs for targeted drug delivery. Angewandte Chemie International Edition, 2011, 50(3): 640–643

    Article  Google Scholar 

  75. Luo G F, Chen W H, Liu Y, et al. Multifunctional enveloped mesoporous silica nanoparticles for subcellular co-delivery of drug and therapeutic peptide. Scientific Reports, 2014, 4: 6064

    Article  Google Scholar 

  76. Li H, Zhang J Z, Tang Q, et al. Reduction-responsive drug delivery based on mesoporous silica nanoparticle core with crosslinked poly(acrylic acid) shell. Materials Science and Engineering C, 2013, 33(6): 3426–3431

    Article  Google Scholar 

  77. Luo Z, Cai K, Hu Y, et al. Redox-responsive molecular nanoreservoirs for controlled intracellular anticancer drug delivery based on magnetic nanoparticles. Advanced Materials, 2012, 24(3): 431–435

    Article  Google Scholar 

  78. Wen H, Dong C, Dong H, et al. Engineered redox-responsive PEG detachment mechanism in PEGylated nano-graphene oxide for intracellular drug delivery. Small, 2012, 8(5): 760–769

    Article  Google Scholar 

  79. Zhao X, Yang L, Li X, et al. Functionalized graphene oxide nanoparticles for cancer cell-specific delivery of antitumor drug. Bioconjugate Chemistry, 2015, 26(1): 128–136

    Article  Google Scholar 

  80. Saito G, Swanson J A, Lee K D. Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Advanced Drug Delivery Reviews, 2003, 55(2): 199–215

    Article  Google Scholar 

  81. Li X Q, Wen H Y, Dong H Q, et al. Self-assembling nanomicelles of a novel camptothecin prodrug engineered with a redoxresponsive release mechanism. Chemical Communications, 2011, 47(30): 8647–8649

    Article  Google Scholar 

  82. Liu C, Yuan J, Luo X, et al. Folate-decorated and reduction-sensitive micelles assembled from amphiphilic polymer-camptothecin conjugates for intracellular drug delivery. Molecular Pharmaceutics, 2014, 11(11): 4258–4269

    Article  Google Scholar 

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  1. State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China

    Lei Liu & Peng Liu

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Liu, L., Liu, P. Synthesis strategies for disulfide bond-containing polymer-based drug delivery system for reduction-responsive controlled release. Front. Mater. Sci. 9, 211–226 (2015). https://doi.org/10.1007/s11706-015-0283-y

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