Reduction‐responsive polymers for drug delivery in cancer therapy—Is there anything new to discover?

Advanced Review

Cameron Alexander, Claudia Conte, Alessandra Travanut, Patrícia F. Monteiro

Published Online: Nov 06 2020

DOI: 10.1002/wnan.1678

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Abstract Among various types of stimuli‐responsive drug delivery systems, reduction‐responsive polymers have attracted great interest. In general, these systems have high stability in systemic circulation, however, they can respond quickly to differences in the concentrations of reducing species in specific physiological sites associated with a pathology. This is a particularly relevant strategy to target diseases in which hypoxic regions are present, as polymers which are sensitive to in‐situ expressed antioxidant species can, through a local response, release a therapeutic at high concentration in the targeted site, and thus, improve the selectivity and efficacy of the treatment. At the same time, such reduction‐responsive materials can also decrease the toxicity and side effects of certain drugs. To date, polymers containing disulfide linkages are the most investigated of the class of reduction‐responsive nanocarriers, however, other groups such as selenide and diselenide have also been used for the same purpose. In this review article, we discussed the rationale behind the development of reduction‐responsive polymers as drug delivery systems and highlight examples of recent progress. We include the most popular design methods to generate reduction‐responsive polymeric carriers and their applications in cancer therapy, and question what areas may still need to be explored in a field with already a very large number of research articles. Finally, we consider the main challenges associated with the clinical translation of these nanocarriers and the future perspectives in this area. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

Structures of glutathione in its two states encountered in cells: oxidized glutathione (GSSG) reaction occurring through the glutathione peroxidase and reduced glutathione (GSH) through the reaction leaded by the enzyme glutathione reductase. Structures are presented in their fully protonated forms

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Illustration paclitaxel‐citronellol conjugates containing thioether, disulfide, sulfur, selenoether, diselenide, carbon or carbon–carbon bonds as prodrug nanoassemblies for cancer therapy (Reprinted with permission from B. Sun et al. (2019). Spring Nature 2019)

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Illustration of reduction and pH dual‐sensitive core‐crosslinked lipoic acid and cis‐1,2‐cyclohexanedicarboxylic acid decorated poly(ethylene glycol)‐b‐poly(l‐lysine) micelles for active loading and triggered intracellular release of DOX (Reprinted with permission from L. Wu et al. (2013). Copyright 2013 Elsevier Ltd)

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Illustration of l‐cysteine‐based poly (disulfide amide) (Cys‐PSDA) and intracellular delivery of docetaxel‐loaded redox‐responsive Cys‐PDSA nanoparticles (Reprinted with permission from J. Wu et al. (2015). Copyright 2015 John Wiley and Sons)

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References

Allen,, T. M., & Cullis,, P. R. (2004). Drug delivery systems: Entering the mainstream. Science, 303(5665), 1818–1822. https://doi.org/10.1126/science.1095833
Bansal,, A., & Simon,, M. C. (2018). Glutathione metabolism in cancer progression and treatment resistance. The Journal of Cell Biology, 217(7), 2291–2298. https://doi.org/10.1083/jcb.201804161
Becker,, A. L., Orlotti,, N. I., Folini,, M., Cavalieri,, F., Zelikin,, A. N., Johnston,, A. P. R., … Caruso,, F. (2011). Redox‐active polymer microcapsules for the delivery of a survivin‐specific siRNA in prostate cancer cells. ACS Nano, 5(2), 1335–1344. https://doi.org/10.1021/nn103044z
Benfeitas,, R., Uhlen,, M., Nielsen,, J., & Mardinoglu,, A. (2017). New challenges to study heterogeneity in cancer redox metabolism. Frontiers in Cell and Development Biology, 5, 65. https://doi.org/10.3389/fcell.2017.00065
Biswas,, S., Kumari,, P., Lakhani,, P. M., & Ghosh,, B. (2016). Recent advances in polymeric micelles for anti‐cancer drug delivery. European Journal of Pharmaceutical Sciences, 83, 184–202. https://doi.org/10.1016/j.ejps.2015.12.031
Blakney,, A. K., Zhu,, Y., McKay,, P. F., Bouton,, C. R., Yeow,, J., Tang,, J., … Stevens,, M. M. (2020). Big is beautiful: Enhanced saRNA delivery and immunogenicity by a higher molecular weight, bioreducible, cationic polymer. ACS Nano, 14(5), 5711–5727. https://doi.org/10.1021/acsnano.0c00326
Blanco,, E., Shen,, H., & Ferrari,, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33(9), 941–951. https://doi.org/10.1038/nbt.3330
Bulmus,, V., Woodward,, M., Lin,, L., Murthy,, N., Stayton,, P., & Hoffman,, A. (2003). A new Ph‐responsive and glutathione‐reactive, endosomal membrane‐disruptive polymeric carrier for intracellular delivery of biomolecular drugs. Journal of Controlled Release, 93(2), 105–120.
Calcutt,, G., & Connors,, T. A. (1963). Tumour sulphydryl levels and sensitivity to the nitrogen mustard merophan. Biochemical Pharmacology, 12, 839–845. https://doi.org/10.1016/0006-2952(63)90114-x
Chai,, Z., Teng,, C., Yang,, L., Ren,, L., Yuan,, Z., Xu,, S., … Yin,, L. (2020). Doxorubicin delivered by redox‐responsive hyaluronic acid–ibuprofen prodrug micelles for treatment of metastatic breast cancer. Carbohydrate Polymers, 245, 116527. https://doi.org/10.1016/j.carbpol.2020.116527
Chakravarthi,, S., Jessop,, C. E., & Bulleid,, N. J. (2006). The role of glutathione in disulphide bond formation and endoplasmic‐reticulum‐generated oxidative stress. EMBO Reports, 7(3), 271–275. https://doi.org/10.1038/sj.embor.7400645
Chiang,, Y. T., Yen,, Y. W., & Lo,, C. L. (2015). Reactive oxygen species and glutathione dual redox‐responsive micelles for selective cytotoxicity of cancer. Biomaterials, 61, 150–161. https://doi.org/10.1016/j.biomaterials.2015.05.007
Connors,, T. A. (1966). Protection against the toxicity of alkylating agents by thiols: The mechanism of protection and its relevance to cancer chemotherapy. A Review. European Journal of Cancer, 2(4), 293–305. https://doi.org/10.1016/0014-2964(66)90042-9
Conte,, C., Mastrotto,, F., Taresco,, V., Tchoryk,, A., Quaglia,, F., Stolnik,, S., & Alexander,, C. (2018). Enhanced uptake in 2D‐ and 3D‐ lung cancer cell models of redox responsive PEGylated nanoparticles with sensitivity to reducing extra‐ and intracellular environments. Journal of Controlled Release, 277, 126–141. https://doi.org/10.1016/j.jconrel.2018.03.011
Conway,, J. G., Neptun,, D. A., Garvey,, L. K., & Popp,, J. A. (1987). Carcinogen treatment increases glutathione hydrolysis by gamma‐glutamyl transpeptidase. Carcinogenesis, 8(7), 999–1004. https://doi.org/10.1093/carcin/8.7.999
Cook,, J. A., Pass,, H. I., Iype,, S. N., Friedman,, N., DeGraff,, W., Russo,, A., & Mitchell,, J. B. (1991). Cellular glutathione and thiol measurements from surgically resected human lung tumor and normal lung tissue. Cancer Research, 51(16), 4287–4294 Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1868449
Day,, C. P., Merlino,, G., & Van Dyke,, T. (2015). Preclinical mouse cancer models: A maze of opportunities and challenges. Cell, 163(1), 39–53. https://doi.org/10.1016/j.cell.2015.08.068
Deneke,, S. M., & Fanburg,, B. L. (1989). Regulation of cellular glutathione. The American Journal of Physiology, 257(4 Pt 1, L163–L173. https://doi.org/10.1152/ajplung.1989.257.4.L163
Deng,, B., Ma,, P., & Xie,, Y. (2015). Reduction‐sensitive polymeric nanocarriers in cancer therapy: A comprehensive review. Nanoscale, 7(30), 12773–12795. https://doi.org/10.1039/C5NR02878G
Deng,, Z., Yuan,, S., Xu,, R. X., Liang,, H., & Liu,, S. (2018). Reduction‐triggered transformation of disulfide‐containing micelles at chemically tunable rates. Angewandte Chemie (International Ed. in English), 57(29), 8896–8900. https://doi.org/10.1002/anie.201802909
Diaz‐Cano,, S. J. (2012). Tumor heterogeneity: Mechanisms and bases for a reliable application of molecular marker design. International Journal of Molecular Sciences, 13(2), 1951–2011. https://doi.org/10.3390/ijms13021951
Estrela,, J. M., Ortega,, A., & Obrador,, E. (2006). Glutathione in cancer biology and therapy. Critical Reviews in Clinical Laboratory Sciences, 43(2), 143–181. https://doi.org/10.1080/10408360500523878
Fang,, Y., & Eglen,, R. M. (2017). Three‐dimensional cell cultures in drug discovery and development. SLAS DISCOVERY: Advancing Life Sciences R%26D, 22(5), 456–472. https://doi.org/10.1177/1087057117696795
Forman,, H. J., Zhang,, H., & Rinna,, A. (2009). Glutathione: Overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine, 30(1–2), 1–12. https://doi.org/10.1016/j.mam.2008.08.006
Gaspar,, R., & Duncan,, R. (2009). Polymeric carriers: Preclinical safety and the regulatory implications for design and development of polymer therapeutics. Advanced Drug Delivery Reviews, 61(13), 1220–1231. https://doi.org/10.1016/j.addr.2009.06.003
Gulfam,, M., Matini,, T., Monteiro,, P. F., Riva,, R., Collins,, H., Spriggs,, K., … Alexander,, C. (2017). Bioreducible cross‐linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells. Biomaterials Science, 5(3), 532–550. https://doi.org/10.1039/c6bm00888g
Guo,, X., Cheng,, Y., Zhao,, X., Luo,, Y., Chen,, J., & Yuan,, W. E. (2018). Advances in redox‐responsive drug delivery systems of tumor microenvironment. Journal of Nanobiotechnology, 16(1), 74. https://doi.org/10.1186/s12951-018-0398-2
Han,, X. X., Gong,, F. R., Chi,, L. L., Feng,, C. H., Sun,, J., Chen,, Y. Y., … Shen,, Y. L. (2019). Cancer‐targeted and glutathione‐responsive micellar carriers for controlled delivery of cabazitaxel. Nanotechnology, 30(5), 055601. https://doi.org/10.1088/1361-6528/aaf020
Harington,, J. S. (1967). The sulfhydryl group and carcinogenesis. Advances in Cancer Research, 10, 247–309. https://doi.org/10.1016/s0065-230x(08)60080-9
Hirono,, I. (1961). Mechanism of natural and acquired resistance to methyl‐bis‐(beta‐chlorethyl)‐amine N‐oxide in ascites tumors. Gan, 52, 39–48 Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/13714542
Hu,, Q., Katti,, P. S., & Gu,, Z. (2014). Enzyme‐responsive nanomaterials for controlled drug delivery. Nanoscale, 6(21), 12273–12286. https://doi.org/10.1039/c4nr04249b
Jain,, R. K., & Stylianopoulos,, T. (2010). Delivering nanomedicine to solid tumors. Nature Reviews. Clinical Oncology, 7(11), 653–664 Retrieved from https://doi.org/10.1038/nrclinonc.2010.139
Ji,, S., Cao,, W., Yu,, Y., & Xu,, H. (2014). Dynamic Diselenide bonds: Exchange reaction induced by visible light without catalysis. Angewandte Chemie International Edition, 53(26), 6781–6785. https://doi.org/10.1002/anie.201403442
Jia,, X., He,, J., Shen,, L., Chen,, J., Wei,, Z., Qin,, X., … Shi,, J. (2019). Gradient redox‐responsive and two‐stage rocket‐mimetic drug delivery system for improved tumor accumulation and safe chemotherapy. Nano Letters, 19(12), 8690–8700. https://doi.org/10.1021/acs.nanolett.9b03340
Jiang,, W., Gao,, Y., Wang,, Z., Gong,, C., Hu,, C., Ding,, X., … Ren,, F. (2019). Codelivery of miR‐4638‐5p and Docetaxel based on redox‐sensitive polypeptide micelles as an improved strategy for the treatment of castration‐resistant prostate cancer. Molecular Pharmaceutics, 16(1), 437–447. https://doi.org/10.1021/acs.molpharmaceut.8b01074
Khan,, A. R., Magnusson,, J. P., Watson,, S., Grabowska,, A. M., Wilkinson,, R. W., Alexander,, C., & Pritchard,, D. (2014). Camptothecin prodrug block copolymer micelles with high drug loading and target specificity. Polymer Chemistry, 5(18), 5320–5329. https://doi.org/10.1039/C4PY00369A
Kim,, H., Jeong,, S.‐M., & Park,, J.‐W. (2011). Electrical switching between vesicles and micelles via redox‐responsive self‐assembly of Amphiphilic rod−coils. Journal of the American Chemical Society, 133(14), 5206–5209. https://doi.org/10.1021/ja200297j
Krezel,, A., & Bal,, W. (2003). Structure‐function relationships in glutathione and its analogues. Organic %26 Biomolecular Chemistry, 1(22), 3885–3890. https://doi.org/10.1039/b309306a
Kroemer,, G., & Reed,, J. C. (2000). Mitochondrial control of cell death. Nature Medicine, 6(5), 513–519. https://doi.org/10.1038/74994
Li,, R., & Xie,, Y. (2017). Nanodrug delivery systems for targeting the endogenous tumor microenvironment and simultaneously overcoming multidrug resistance properties. Journal of Controlled Release, 251, 49–67. https://doi.org/10.1016/j.jconrel.2017.02.020
Li,, X. Q., Wen,, H. Y., Dong,, H. Q., Xue,, W. M., Pauletti,, G. M., Cai,, X. J., … Li,, Y. Y. (2011). Self‐assembling nanomicelles of a novel camptothecin prodrug engineered with a redox‐responsive release mechanism. Chemical Communications (Cambridge), 47(30), 8647–8649. https://doi.org/10.1039/c1cc12495a
Liu,, D., Yang,, F., Xiong,, F., & Gu,, N. (2016). The smart drug delivery system and its clinical potential. Theranostics, 6(9), 1306–1323. https://doi.org/10.7150/thno.14858
Locatelli‐Champagne,, C., Suau,, J. M., Guerret,, O., Pellet,, C., & Cloitre,, M. (2017). Versatile encapsulation technology based on tailored pH‐responsive Amphiphilic polymers: Emulsion gels and capsules. Langmuir, 33(49), 14020–14028. https://doi.org/10.1021/acs.langmuir.7b02689
Lu,, Y., Zhang,, E., Yang,, J., & Cao,, Z. (2018). Strategies to improve micelle stability for drug delivery. Nano Research, 11(10), 4985–4998. https://doi.org/10.1007/s12274-018-2152-3
Lv,, M., Li,, S., Zhao,, H., Wang,, K., Chen,, Q., Guo,, Z., … Xue,, W. (2017). Redox‐responsive hyperbranched poly(amido amine) and polymer dots as a vaccine delivery system for cancer immunotherapy. Journal of Materials Chemistry B, 5(48), 9532–9545. https://doi.org/10.1039/C7TB02334K
Ma,, W., Sun,, J., Xu,, J., Luo,, Z., Diao,, D., Zhang,, Z., … Li,, S. (2020). Sensitizing triple negative breast cancer to Tamoxifen chemotherapy via a redox‐responsive Vorinostat‐containing polymeric Prodrug Nanocarrier. Theranostics, 10(6), 2463–2478. https://doi.org/10.7150/thno.38973
Manda,, G., Isvoranu,, G., Comanescu,, M. V., Manea,, A., Debelec Butuner,, B., & Korkmaz,, K. S. (2015). The redox biology network in cancer pathophysiology and therapeutics. Redox Biology, 5, 347–357. https://doi.org/10.1016/j.redox.2015.06.014
Meister,, A. (1983). Selective modification of glutathione metabolism. Science, 220(4596), 472–477. https://doi.org/10.1126/science.6836290
Monteiro,, P. F., Gulfam,, M., Monteiro,, C. J., Travanut,, A., Abelha,, T. F., Pearce,, A. K., … Alexander,, C. (2020). Synthesis of micellar‐like terpolymer nanoparticles with reductively‐cleavable cross‐links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer. Journal of Controlled Release, 323, 549–564. https://doi.org/10.1016/j.jconrel.2020.04.049
Moore,, T., Le,, A., Niemi,, A. K., Kwan,, T., Cusmano‐Ozog,, K., Enns,, G. M., & Cowan,, T. M. (2013). A new LC‐MS/MS method for the clinicaldetermination of reduced and oxidized glutathione from whole blood. J Chromatogr B Analyt Technol Biomed LifeSci, 929, 51–55. https://doi.org/10.1016/j.jchromb.2013.04.004
Mura,, S., Nicolas,, J., & Couvreur,, P. (2013). Stimuli‐responsive nanocarriers for drug delivery. Nature Materials, 12(11), 991–1003. https://doi.org/10.1038/nmat3776
Nie,, S., Xing,, Y., Kim,, G. J., & Simons,, J. W. (2007). Nanotechnology applications in cancer. Annual Review of Biomedical Engineering, 9(1), 257–288. https://doi.org/10.1146/annurev.bioeng.9.060906.152025
Owen,, S. C., Chan,, D. P. Y., & Shoichet,, M. S. (2012). Polymeric micelle stability. Nano Today, 7(1), 53–65. https://doi.org/10.1016/j.nantod.2012.01.002
Patra,, J. K., Das,, G., Fraceto,, L. F., Campos,, E. V. R., Rodriguez‐Torres,, M. D. P., Acosta‐Torres,, L. S., … Shin,, H. S. (2018). Nano based drug delivery systems: Recent developments and future prospects. Journal of Nanobiotechnology, 16(1), 71. https://doi.org/10.1186/s12951-018-0392-8
Pelaz,, B., Alexiou,, C., Alvarez‐Puebla,, R. A., Alves,, F., Andrews,, A. M., Ashraf,, S., … Parak,, W. J. (2017). Diverse applications of nanomedicine. ACS Nano, 11(3), 2313–2381. https://doi.org/10.1021/acsnano.6b06040
Perry,, R. R., Mazetta,, J. A., Levin,, M., & Barranco,, S. C. (1993). Glutathione levels and variability in breast tumors and normal tissue. Cancer, 72(3), 783–787. https://doi.org/10.1002/1097-0142(19930801)72:3%3C783::aid-cncr2820720325%3E3.0.co;2-u
Pizzorno,, J. (2014). Glutathione! Integrative Medicine (Encinitas, Calif.), 13(1), 8–12 Retrieved from https://pubmed.ncbi.nlm.nih.gov/26770075
Qiao,, Y., Wan,, J., Zhou,, L., Ma,, W., Yang,, Y., Luo,, W., … Wang,, H. (2019). Stimuli‐responsive nanotherapeutics for precision drug delivery and cancer therapy. WIREs Nanomedicine and Nanobiotechnology, 11(1), e1527. https://doi.org/10.1002/wnan.1527
Qu,, Y., Chu,, B., Wei,, X., Lei,, M., Hu,, D., Zha,, R., … Qian,, Z. (2019). Redox/pH dual‐stimuli responsive camptothecin prodrug nanogels for “on‐demand” drug delivery. Journal of Controlled Release, 296, 93–106. https://doi.org/10.1016/j.jconrel.2019.01.016
Quinn,, J. F., Whittaker,, M. R., & Davis,, T. P. (2017). Glutathione responsive polymers and their application in drug delivery systems. Polymer Chemistry, 8(1), 97–126. https://doi.org/10.1039/C6PY01365A
Rao,, N. V., Ko,, H., Lee,, J., & Park,, J. H. (2018). Recent Progress and advances in stimuli‐responsive polymers for cancer therapy. Frontiers in Bioengineering and Biotechnology, 6, 110. https://doi.org/10.3389/fbioe.2018.00110
Riber,, C. F., Smith,, A. A. A., & Zelikin,, A. N. (2015). Self‐Immolative linkers literally bridge disulfide chemistry and the realm of Thiol‐free drugs. Advanced Healthcare Materials, 4(12), 1887–1890. https://doi.org/10.1002/adhm.201500344
Ruan,, Z., Yuan,, P., Li,, T., Tian,, Y., Cheng,, Q., & Yan,, L. (2019). Redox‐responsive prodrug‐like PEGylated macrophotosensitizer nanoparticles for enhanced near‐infrared imaging‐guided photodynamic therapy. European Journal of Pharmaceutics and Biopharmaceutics, 135, 25–35. https://doi.org/10.1016/j.ejpb.2018.12.006
Sauraj,, Vinay,, K., Kumar,, B., Priyadarshi,, R., Deeba,, F., Kulshreshtha,, A., … Negi,, Y. S. (2020). Redox responsive xylan‐SS‐curcumin prodrug nanoparticles for dual drug delivery in cancer therapy. Materials Science %26 Engineering. C, Materials for Biological Applications, 107, 110356. https://doi.org/10.1016/j.msec.2019.110356
Senapati,, S., Mahanta,, A. K., Kumar,, S., & Maiti,, P. (2018). Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduction and Targeted Therapy, 3(1), 7. https://doi.org/10.1038/s41392-017-0004-3
Shi,, C., Guo,, X., Qu,, Q., Tang,, Z., Wang,, Y., & Zhou,, S. (2014). Actively targeted delivery of anticancer drug to tumor cells by redox‐responsive star‐shaped micelles. Biomaterials, 35(30), 8711–8722. https://doi.org/10.1016/j.biomaterials.2014.06.036
Shi,, J., Votruba,, A. R., Farokhzad,, O. C., & Langer,, R. (2010). Nanotechnology in drug delivery and tissue engineering: From discovery to applications. Nano Letters, 10(9), 3223–3230. https://doi.org/10.1021/nl102184c
Soliman,, M., Nasanit,, R., Abulateefeh,, S. R., Allen,, S., Davies,, M. C., Briggs,, S. S., … Alexander,, C. (2012). Multicomponent synthetic polymers with viral‐mimetic chemistry for nucleic acid delivery. Molecular Pharmaceutics, 9(1), 1–13. https://doi.org/10.1021/mp200108q
Steghens,, J.‐P., Flourié,, F., Arab,, K., & Collombel,, C. (2003). Fast liquid chromatography–mass spectrometry glutathione measurement inwhole blood: micromolar GSSG is a sample preparation artifact. Journal of Chromatography B, 798(2), 343–349. https://doi.org/10.1016/j.jchromb.2003.10.007
Sun,, B., Luo,, C., Zhang,, X., Guo,, M., Sun,, M., Yu,, H., … Sun,, J. (2019). Probing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy. Nature Communications, 10(1), 3211. https://doi.org/10.1038/s41467-019-11193-x
Sun,, J., Wan,, Z., Chen,, Y., Xu,, J., Luo,, Z., Parise,, R. A., … Li,, S. (2020). Triple drugs co‐delivered by a small gemcitabine‐based carrier for pancreatic cancer immunochemotherapy. Acta Biomaterialia, 106, 289–300. https://doi.org/10.1016/j.actbio.2020.01.039
Suzukake,, K., Vistica,, B. P., & Vistica,, D. T. (1983). Dechlorination of L‐phenylalanine mustard by sensitive and resistant tumor cells and its relationship to intracellular glutathione content. Biochemical Pharmacology, 32, 165–167.
Talelli,, M., Barz,, M., Rijcken,, C. J., Kiessling,, F., Hennink,, W. E., & Lammers,, T. (2015). Core‐Crosslinked polymeric micelles: Principles, preparation, biomedical applications and clinical translation. Nano Today, 10(1), 93–117. https://doi.org/10.1016/j.nantod.2015.01.005
Tang,, X., Gong,, X., Li,, A., Lin,, H., Peng,, C., Zhang,, X., … Gao,, J. (2020). Cascaded multiresponsive self‐assembled 19F MRI Nanoprobes with redox‐triggered activation and NIR‐induced amplification. Nano Letters, 20(1), 363–371. https://doi.org/10.1021/acs.nanolett.9b04016
Tellez‐Gabriel,, M., Ory,, B., Lamoureux,, F., Heymann,, M. F., & Heymann,, D. (2016). Tumour heterogeneity: The key advantages of single‐cell analysis. International Journal of Molecular Sciences, 17(12), 2142–2161. https://doi.org/10.3390/ijms17122142
Townsend,, D. M., Tew,, K. D., & Tapiero,, H. (2003). The importance of glutathione in human disease. Biomedicine %26 Pharmacotherapy, 57(3–4), 145–155. https://doi.org/10.1016/s0753-3322(03)00043-x
Trachootham,, D., Lu,, W., Ogasawara,, M. A., Nilsa,, R. D., & Huang,, P. (2008). Redox regulation of cell survival. Antioxidants %26 Redox Signaling, 10(8), 1343–1374. https://doi.org/10.1089/ars.2007.1957
Traitel,, T., Goldbart,, R., & Kost,, J. (2008). Smart polymers for responsive drug‐delivery systems. Journal of Biomaterials Science. Polymer Edition, 19(6), 755–767. https://doi.org/10.1163/156856208784522065
Ulrich,, K., & Jakob,, U. (2019). The role of thiols in antioxidant systems. Free Radical Biology %26 Medicine, 140, 14–27. https://doi.org/10.1016/j.freeradbiomed.2019.05.035
Wang,, X., He,, C., Yang,, Q., Tan,, L., Liu,, B., Zhu,, Z., … Shen,, Y. M. (2017). Dynamic covalent linked triblock copolymer micelles for glutathione‐mediated intracellular drug delivery. Materials Science %26 Engineering. C, Materials for Biological Applications, 77, 34–44. https://doi.org/10.1016/j.msec.2017.03.240
Wilhelm,, S., Tavares,, A. J., Dai,, Q., Ohta,, S., Audet,, J., Dvorak,, H. F., & Chan,, W. C. W. (2016). Analysis of nanoparticle delivery to tumours. Nature Reviews Materials, 1(5), 16014. https://doi.org/10.1038/natrevmats.2016.14
Wohl,, B. M., Smith,, A. A. A., Jensen,, B. E. B., & Zelikin,, A. N. (2014). Macromolecular (pro)drugs with concurrent direct activity against the hepatitis C virus and inflammation. Journal of Controlled Release, 196, 197–207. https://doi.org/10.1016/j.jconrel.2014.09.032
Wu,, G., Fang,, Y. Z., Yang,, S., Lupton,, J. R., & Turner,, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489–492. https://doi.org/10.1093/jn/134.3.489
Wu,, J., Zhao,, L., Xu,, X., Bertrand,, N., Choi,, W. I., Yameen,, B., … Farokhzad,, O. C. (2015). Hydrophobic cysteine poly(disulfide)‐based redox‐hypersensitive nanoparticle platform for cancer Theranostics. Angewandte Chemie (International Ed. in English), 54(32), 9218–9223. https://doi.org/10.1002/anie.201503863
Wu,, L., Zou,, Y., Deng,, C., Cheng,, R., Meng,, F., & Zhong,, Z. (2013). Intracellular release of doxorubicin from core‐crosslinked polypeptide micelles triggered by both pH and reduction conditions. Biomaterials, 34(21), 5262–5272. https://doi.org/10.1016/j.biomaterials.2013.03.035
Wu,, Z., Gan,, Z., Chen,, B., Chen,, F., Cao,, J., & Luo,, X. (2019). pH/redox dual‐responsive amphiphilic zwitterionic polymers with a precisely controlled structure as anti‐cancer drug carriers. Biomaterials Science, 7(8), 3190–3203. https://doi.org/10.1039/c9bm00407f
Xia,, J., Du,, Y., Huang,, L., Chaurasiya,, B., Tu,, J., Webster,, T. J., & Sun,, C. (2018). Redox‐responsive micelles from disulfide bond‐bridged hyaluronic acid‐tocopherol succinate for the treatment of melanoma. Nanomedicine, 14(3), 713–723. https://doi.org/10.1016/j.nano.2017.12.017
Yang,, H., Wang,, Q., Li,, Z., Li,, F., Wu,, D., Fan,, M., … Yang,, X. (2018). Hydrophobicity‐adaptive Nanogels for programmed anticancer drug delivery. Nano Letters, 18(12), 7909–7918. https://doi.org/10.1021/acs.nanolett.8b03828
Yin,, T., Wang,, Y., Chu,, X., Fu,, Y., Wang,, L., Zhou,, J., … Huo,, M. (2018). Free Adriamycin‐loaded pH/reduction dual‐responsive hyaluronic acid‐Adriamycin Prodrug micelles for efficient cancer therapy. ACS Applied Materials %26 Interfaces, 10(42), 35693–35704. https://doi.org/10.1021/acsami.8b09342
Yin,, W., Ke,, W., Lu,, N., Wang,, Y., Japir,, A. A.‐W. M. M., Mohammed,, F., … Ge,, Z. (2020). Glutathione and reactive oxygen species dual‐responsive block copolymer Prodrugs for boosting tumor site‐specific drug release and enhanced antitumor efficacy. Biomacromolecules, 21(2), 921–929. https://doi.org/10.1021/acs.biomac.9b01578
Yu,, L., Zhang,, M., Du,, F.‐S., & Li,, Z.‐C. (2018). ROS‐responsive poly(ε‐caprolactone) with pendent thioether and selenide motifs. Polymer Chemistry, 9(27), 3762–3773. https://doi.org/10.1039/C8PY00620B
Zhai,, S., Hu,, X., Hu,, Y., Wu,, B., & Xing,, D. (2017). Visible light‐induced crosslinking and physiological stabilization of diselenide‐rich nanoparticles for redox‐responsive drug release and combination chemotherapy. Biomaterials, 121, 41–54. https://doi.org/10.1016/j.biomaterials.2017.01.002
Zhang,, L., Liu,, W., Lin,, L., Chen,, D., & Stenzel,, M. H. (2008). Degradable disulfide Core‐cross‐linked micelles as a drug delivery system prepared from vinyl functionalized nucleosides via the RAFT process. Biomacromolecules, 9(11), 3321–3331. https://doi.org/10.1021/bm800867n
Zhang,, L., Liu,, Y., Zhang,, K., Chen,, Y., & Luo,, X. (2019). Redox‐responsive comparison of diselenide micelles with disulfide micelles. Colloid and Polymer Science, 297(2), 225–238. https://doi.org/10.1007/s00396-018-4457-x
Zhang,, L., Zhou,, Y., Shi,, G., Sang,, X., & Ni,, C. (2017). Preparations of hyperbranched polymer nano micelles and the pH/redox controlled drug release behaviors. Materials Science %26 Engineering. C, Materials for Biological Applications, 79, 116–122. https://doi.org/10.1016/j.msec.2017.05.027
Zhang,, M., Song,, C.‐C., Ji,, R., Qiao,, Z.‐Y., Yang,, C., Qiu,, F.‐Y., … Li,, Z.‐C. (2016). Oxidation and temperature dual responsive polymers based on phenylboronic acid and N‐isopropylacrylamide motifs. Polymer Chemistry, 7(7), 1494–1504. https://doi.org/10.1039/C5PY01999K
Zhang,, X., Kang,, Y., Liu,, G. T., Li,, D. D., Zhang,, J. Y., Gu,, Z. P., & Wu,, J. (2019). Poly(cystine‐PCL) based pH/redox dual‐responsive nanocarriers for enhanced tumor therapy. Biomaterials Science, 7(5), 1962–1972. https://doi.org/10.1039/c9bm00009g

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