journal article·2021-03

Research progress of response strategies based on tumor microenvironment in drug delivery systems

Xiu’e Li, Xiaotong Yang, Rongxia Wu, Naijun Dong, Xiumei Lu, Peng Zhang

Journal of Nanoparticle Research· Volume 23· Issue 3
Publisher page

Abstract

In recent years, nanomedicines have shown tremendous progress in their targeted delivery systems and effective anticancer functions. The targeting, solubility, chemical stability, and degradability of nanocarriers make them widely used. The tumor microenvironment is different from that of normal cells. According to the response characteristics of pH, reducibility, hypoxia, reactive oxygen species, and enzymes, a series of tumor microenvironment stimulation–responsive nanocarrier delivery platforms were constructed.
Source: openaire · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Nanoparticle-Based Drug Delivery · Nanoplatforms for cancer theranostics · RNA Interference and Gene Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (75)

Show source-provided references
1. Aberoumandi S, Mohammadhosseini M, Abasi E, Saghati S, Nikzamir N, Akbarzadeh A, Panahi Y, Davaran S (2017) An update on applications of nanostructured drug delivery systems in cancer therapy: a review. Artif Cells Nanomed Biotechnol 45(6):1–11. https://doi.org/10.1080/21691401.2016.122865810.1080/21691401.2016.1228658 ↗
2. An N, Lin HM, Yang CY, Zhang T, Tong RH, Chen YH, Qu FY (2016) Gated magnetic mesoporous silica nanoparticles for intracellular enzyme-triggered drug delivery. Mater Sci Eng C Mater Biol Appl 69:292–300. https://doi.org/10.1016/j.msec.2016.06.08610.1016/j.msec.2016.06.086 ↗
3. Baskar R, Lee KA, Yeo R, Yeoh KW (2012) Cancer and radiation therapy: current advances and future directions. Int J Med Sci 9(3):193–199. https://doi.org/10.7150/ijms.363510.7150/ijms.3635 ↗
4. Behroozi F, Abdkhodaie MJ, Abandansari HS, Satarian L, Molazem M, Al-Jamal KT, Baharvand H (2018) Engineering folate-targeting diselenide-containing triblock copolymer as a redox-responsive shell-sheddable micelle for antitumor therapy in vivo. Acta Biomater 76:239–256. https://doi.org/10.1016/j.actbio.2018.05.03110.1016/j.actbio.2018.05.031 ↗
5. Boisselier E, Astruc D (2009) Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 38(6):1759–1782. https://doi.org/10.1039/b806051g10.1039/b806051g ↗
6. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.2149210.3322/caac.21492 ↗
7. Burda C, Chen XB, Narayanan R, El-Sayed MA (2005) Chemistry and properties of nanocrystals of different shapes. Chem Rev 105(4):1025–1102. https://doi.org/10.1021/cr030063a10.1021/cr030063a ↗
8. Cai J, Fu JR, Li RR, Zhang F, Ling GX, Zhang P (2019) A potential carrier for anti-tumor targeted delivery-hyaluronic acid nanoparticles. Carbohydr Polym 208:356–364. https://doi.org/10.1016/j.carbpol.2018.12.07410.1016/j.carbpol.2018.12.074 ↗
9. Chang S, Wang YF, Zhang TY, Pu XH, Zong LL, Zhu HY, Zhao LL, Feng B (2019) Redox-responsive disulfide bond-bridged mPEG-PBLA prodrug micelles for enhanced paclitaxel biosafety and antitumor efficacy. Front Oncol 9. https://doi.org/10.3389/fonc.2019.0082310.3389/fonc.2019.00823 ↗
10. Chen Y, Ai KL, Liu JH, Sun GY, Yin Q, Lu LH (2015) Multifunctional envelope-type mesoporous silica nanoparticles for pH-responsive drug delivery and magnetic resonance imaging. Biomaterials 60:111–120. https://doi.org/10.1016/j.biomaterials.2015.05.00310.1016/j.biomaterials.2015.05.003 ↗
11. Chen Q, Liu GX, Liu S, Su HY, Wang Y, Li JY, Luo C (2018) Remodeling the tumor microenvironment with emerging nanotherapeutics. Trends Pharmacol Sci 39(1):59–74. https://doi.org/10.1016/j.tips.2017.10.00910.1016/j.tips.2017.10.009 ↗
12. Cheng YJ, Luo GF, Zhu JY, Xu XD, Zeng X, Cheng DB, Li YM, Wu Y, Zhang XZ, Zhuo RX, He F (2015) Enzyme-induced and tumor-targeted drug delivery system based on multifunctional mesoporous silica nanoparticles. ACS Appl Mater Interfaces 7(17):9078–9087. https://doi.org/10.1021/acsami.5b0075210.1021/acsami.5b00752 ↗
13. Chiang YT, Yen YW, Lo CL (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.2015.05.00710.1016/j.biomaterials.2015.05.007 ↗
14. Cotrin SS, Puzer L, Judice WAD, Juliano L, Carmona AK, Juliano MA (2004) Positional-scanning combinatorial libraries of fluorescence resonance energy transfer peptides to define substrate specificity of carboxydipeptidases: assays with human cathepsin B. Anal Biochem 335(2):244–252. https://doi.org/10.1016/j.ab.2004.09.01210.1016/j.ab.2004.09.012 ↗
15. de la Torre C, Mondragon L, Coll C, Sancenon F, Marcos MD, Martinez-Manez R, Amoros P, Perez-Paya E, Orzaez M (2014) Cathepsin-B induced controlled release from peptide-capped mesoporous silica nanoparticles. Chem Eur J 20(47):15309–15314. https://doi.org/10.1002/chem.20140438210.1002/chem.201404382 ↗
16. Deirram N, Zhang CH, Kermaniyan SS, Johnston APR, Such GK (2019) pH-responsive polymer nanoparticles for drug delivery. Macromol Rapid Commun 40(10):1800917. https://doi.org/10.1002/marc.20180091710.1002/marc.201800917 ↗
17. Deslongchamps P, Dory YL, Li SG (2000) The relative rate of hydrolysis of a series of acyclic and six-membered cyclic acetals, ketals, orthoesters, and orthocarbonates. Tetrahedron 56(22):3533–3537. https://doi.org/10.1016/s0040-4020(00)00270-210.1016/s0040-4020(00)00270-2 ↗
18. Doane TL, Burda C (2012) The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy. Chem Soc Rev 41(7):2885–2911. https://doi.org/10.1039/c2cs15260f10.1039/c2cs15260f ↗
19. Dong CY, Zhou Q, Xiang JJ, Liu FS, Zhou ZX, Shen YQ (2020) Self-assembly of oxidation-responsive polyethylene glycol-paclitaxel prodrug for cancer chemotherapy. J Control Release 321:529–539. https://doi.org/10.1016/j.jconrel.2020.02.03810.1016/j.jconrel.2020.02.038 ↗
20. Fang Y, Xue JX, Gao S, Lu AQ, Yang DJ, Jiang H, He Y, Shi K (2017) Cleavable PEGylation: a strategy for overcoming the “PEG dilemma” in efficient drug delivery. Drug Deliv 24(2):22–32. https://doi.org/10.1080/10717544.2017.138845110.1080/10717544.2017.1388451 ↗
21. Gao WW, Hu CMJ, Fang RH, Zhang LF (2013) Liposome-like nanostructures for drug delivery. J Mater Chem B 1(48):6569–6585. https://doi.org/10.1039/c3tb21238f10.1039/c3tb21238f ↗
22. Gilkes DM, Semenza GL, Wirtz D (2014) Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer 14(6):430–439. https://doi.org/10.1038/nrc372610.1038/nrc3726 ↗
23. Graf N, Lippard SJ (2012) Redox activation of metal-based prodrugs as a strategy for drug delivery. Adv Drug Deliv Rev 64(11):993–1004. https://doi.org/10.1016/j.addr.2012.01.00710.1016/j.addr.2012.01.007 ↗
24. Habibi N, Kamaly N, Memic A, Shafiee H (2016) Self-assembled peptide-based nanostructures: smart nanomaterials toward targeted drug delivery. Nano Today 11(1):41–60. https://doi.org/10.1016/j.nantod.2016.02.00410.1016/j.nantod.2016.02.004 ↗
25. Hall MD, Failes TW, Yamamoto N, Hambley TW (2007) Bioreductive activation and drug chaperoning in cobalt pharmaceuticals. Dalton Trans 36:3983–3990. https://doi.org/10.1039/b707121c10.1039/b707121c ↗
26. Hinds G, Thomas VD (2008) Malignancy and cancer treatment-related hair and nail changes. Dermatol Clin 26(1):59−+. https://doi.org/10.1016/j.det.2007.08.00310.1016/j.det.2007.08.003 ↗
27. Hsu PP, Sabatini DM (2008) Cancer cell metabolism: Warburg and beyond. Cell 134(5):703–707. https://doi.org/10.1016/j.cell.2008.08.02110.1016/j.cell.2008.08.021 ↗
28. Hu JJ, Lei Q, Peng MY, Zheng DW, Chen YX, Zhang XZ (2017) A positive feedback strategy for enhanced chemotherapy based on ROS-triggered self-accelerating drug release nanosystem. Biomaterials 128:136–146. https://doi.org/10.1016/j.biomaterials.2017.03.01010.1016/j.biomaterials.2017.03.010 ↗
29. Jang EH, Kim GL, Park MG, Shim MK, Kim J-H (2020) Hypoxia-responsive, organic -inorganic hybrid mesoporous silica nanoparticles for triggered drug release. J Drug Deliv Sci Technol 56. https://doi.org/10.1016/j.jddst.2020.10154310.1016/j.jddst.2020.101543 ↗
30. Kanamala M, Palmer BD, Ghandehari H, Wilson WR, Wu ZM (2018) PEG-benzaldehyde-hydrazone-lipid based PEG-Sheddable pH-sensitive liposomes: abilities for endosomal escape and Long circulation. Pharm Res 35(8). https://doi.org/10.1007/s11095-018-2429-y10.1007/s11095-018-2429-y ↗
31. Khatoon S, Han HS, Jeon J, Rao NV, Jeong DW, Ikram M, Yasin T, Yi GR, Park JH (2018) Hypoxia-responsive mesoporous nanoparticles for doxorubicin delivery. Polymers 10(4). https://doi.org/10.3390/polym1004039010.3390/polym10040390 ↗
32. Kievit FM, Zhang MQ (2011) Surface engineering of Iron oxide nanoparticies for targeted cancer therapy. Acc Chem Res 44(10):853–862. https://doi.org/10.1021/ar200027710.1021/ar2000277 ↗
33. Kim SW, Oh KT, Youn YS, Lee ES (2014) Hyaluronated nanoparticles with pH- and enzyme-responsive drug release properties. Colloids Surf B Biointerfaces 116:359–364. https://doi.org/10.1016/j.colsurfb.2014.01.01710.1016/j.colsurfb.2014.01.017 ↗
34. Kim YS, Kim S, Kang HC, Shim MS (2019) ROS-responsive thioether-based nanocarriers for efficient pro-oxidant cancer therapy. J Ind Eng Chem 75:238–245. https://doi.org/10.1016/j.jiec.2019.03.03010.1016/j.jiec.2019.03.030 ↗
35. Kuang TR, Liu YR, Gong TT, Peng XF, Hu XL, Yu ZQ (2016) Enzyme-responsive nanoparticles for anticancer drug delivery. Curr Nanosci 12(1):38–46. https://doi.org/10.2174/157341371166615062417051810.2174/1573413711666150624170518 ↗
36. Li Y, Lu AL, Long MM, Cui L, Chen ZP, Zhu L (2019) Nitroimidazole derivative incorporated liposomes for hypoxia-triggered drug delivery and enhanced therapeutic efficacy in patient-derived tumor xenografts. Acta Biomater 83:334–348. https://doi.org/10.1016/j.actbio.2018.10.02910.1016/j.actbio.2018.10.029 ↗
37. Li RR, Peng FF, Cai J, Yang DD, Zhang P (2020) Redox dual-stimuli responsive drug delivery systems for improving tumor-targeting ability and reducing adverse side effects. Asian J Pharm Sci 15(3):311–325. https://doi.org/10.1016/j.ajps.2019.06.00310.1016/j.ajps.2019.06.003 ↗
38. Liang J, Liu B (2016) ROS-responsive drug delivery systems. Bioeng Transl Med 1(3):239–251. https://doi.org/10.1002/btm2.1001410.1002/btm2.10014 ↗
39. Liang YQ, Li SX, Wang XL, Zhang Y, Sun YN, Wang YQ, Wang XY, He B, Dai WB, Zhang H, Wang XQ, Zhang Q (2018) A comparative study of the antitumor efficacy of peptide-doxorubicin conjugates with different linkers. J Control Release 275:129–141. https://doi.org/10.1016/j.jconrel.2018.01.03310.1016/j.jconrel.2018.01.033 ↗
40. Lim EK, Chung BH, Chung SJ (2018) Recent advances in pH-sensitive polymeric nanoparticles for smart drug delivery in cancer therapy. Curr Drug Targets 19(4):300–317. https://doi.org/10.2174/138945011766616060220233910.2174/1389450117666160602202339 ↗
41. Louage B, van Steenbergen MJ, Nuhn L, Risseeuw MDP, Karalic I, Winne J, Van Calenbergh S, Hennik WE, De Geest BG (2017) Micellar paclitaxel-initiated RAFT polymer conjugates with acid-sensitive behavior. ACS Macro Lett 6(3):272–276. https://doi.org/10.1021/acsmacrolett.6b0097710.1021/acsmacrolett.6b00977 ↗
42. Luo WB, Wang YF (2019) Hypoxia mediates tumor malignancy and therapy resistance. Hypoxia and Cancer Metastasis 1136:1–18. https://doi.org/10.1007/978-3-030-12734-3_110.1007/978-3-030-12734-3_1 ↗
43. Luo C, Sun BJ, Wang C, Zhang XB, Chen Y, Chen Q, Yu H, Zhao HQ, Sun MC, Li ZB, Zhang HT, Kan QM, Wang YJ, He ZG, Sun J (2019) Self-facilitated ROS-responsive nanoassembly of heterotypic dimer for synergistic chemo-photodynamic therapy. J Control Release 302:79–89. https://doi.org/10.1016/j.jconrel.2019.04.00110.1016/j.jconrel.2019.04.001 ↗
44. Lux CD, Joshi-Barr S, Nguyen T, Mahmoud E, Schopf E, Fomina N, Almutairi A (2012) Biocompatible polymeric nanoparticles degrade and release cargo in response to biologically relevant levels of hydrogen peroxide. J Am Chem Soc 134(38):15758–15764. https://doi.org/10.1021/ja303372u10.1021/ja303372u ↗
45. Mo R, Gu Z (2016) Tumor microenvironment and intracellular signal-activated nanomaterials for anticancer drug delivery. Mater Today 19(5):274–283. https://doi.org/10.1016/j.mattod.2015.11.02510.1016/j.mattod.2015.11.025 ↗
46. Nam J, Won N, Bang J, Jin H, Park J, Jung S, Jung S, Park Y, Kim S (2013) Surface engineering of inorganic nanoparticles for imaging and therapy. Adv Drug Deliv Rev 65(5):622–648. https://doi.org/10.1016/j.addr.2012.08.01510.1016/j.addr.2012.08.015 ↗
47. Nicolas J (2016) Drug-initiated synthesis of polymer prodrugs: combining simplicity and efficacy in drug delivery. Chem Mater 28(6):1591–1606. https://doi.org/10.1021/acs.chemmater.5b0428110.1021/acs.chemmater.5b04281 ↗
48. Ou KY, Xu XJ, Guan SY, Zhang RH, Zhang XY, Kang Y, Wu J (2020) Nanodrug carrier based on poly(ursolic acid) with self-anticancer activity against colorectal cancer. Adv Funct Mater 30(9):1907857. https://doi.org/10.1002/adfm.20190785710.1002/adfm.201907857 ↗
49. Oun R, Moussa YE, Wheate NJ (2018) The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans 47(19):6645–6653. https://doi.org/10.1039/c8dt00838h10.1039/c8dt00838h ↗
50. Peer D, Karp JM, Hong S, FaroKhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760. https://doi.org/10.1038/nnano.2007.38710.1038/nnano.2007.387 ↗
51. Peng X, Yang C, Kong X, Xiang Y, Dai W, Quan H (2020a) Multifunctional nanocomposites MGO/FU-MI inhibit the proliferation of tumor cells and enhance the effect of chemoradiotherapy in vivo and in vitro. Clin Transl Oncol 22(10):1875–1884. https://doi.org/10.1007/s12094-020-02331-910.1007/s12094-020-02331-9 ↗
52. Peng FF, Li RR, Zhang F, Qin L, Ling GX, Zhang P (2020b) Potential drug delivery nanosystems for improving tumor penetration. Eur J Pharm Biopharm 151:220–238. https://doi.org/10.1016/j.ejpb.2020.04.00910.1016/j.ejpb.2020.04.009 ↗
53. Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, Castoria G, Migliaccio A (2020) ROS in cancer therapy: the bright side of the moon. Exp Mol Med 52(2):192–203. https://doi.org/10.1038/s12276-020-0384-210.1038/s12276-020-0384-2 ↗
54. Plumb JA, Bilsland A, Kakani R, Zhao J, Glasspool RM, Knox RJ, Evans TR, Keith WN (2001) Telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954. Oncogene 20(53):7797–7803. https://doi.org/10.1038/sj.onc.120495410.1038/sj.onc.1204954 ↗
55. Pu XH, Zhao LL, Li J, Song RF, Wang YL, Yu KK, Hou XQ, Qiao P, Zong LL, Chang S (2019) A polymeric micelle with an endosomal pH-sensitivity for intracellular delivery and enhanced antitumor efficacy of hydroxycamptothecin. Acta Biomater 88:357–369. https://doi.org/10.1016/j.actbio.2019.02.03910.1016/j.actbio.2019.02.039 ↗
56. Rad AT, Chen CW, Aresh W, Xia Y, Lai PS, Nieh MP (2019) Combinational effects of active targeting, shape, and enhanced permeability and retention for cancer theranostic nanocarriers. ACS Appl Mater Interfaces 11(11):10505–10519. https://doi.org/10.1021/acsami.8b2160910.1021/acsami.8b21609 ↗
57. Riehemann K, Schneider SW, Luger TA, Godin B, Ferrari M, Fuchs H (2009) Nanomedicine-challenge and perspectives. Angew Chem Int Ed Engl 48(5):872–897. https://doi.org/10.1002/anie.20080258510.1002/anie.200802585 ↗
58. Saito G, Swanson JA, Lee KD (2003) Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv Drug Deliv Rev 55(2):199–215. https://doi.org/10.1016/s0169-409x(02)00179-510.1016/s0169-409x(02)00179-5 ↗
59. Sedlacek O, Monnery BD, Mattova J, Kucka J, Panek J, Janouskova O, Hocherl A, Verbraeken B, Vergaelen M, Zadinova M, Hoogenboom R, Hruby M (2017) Poly(2-ethyl-2-oxazoline) conjugates with doxorubicin for cancer therapy: in vitro and in vivo evaluation and direct comparison to poly N-(2-hydroxypropyl)methacrylamide analogues. Biomaterials 146:1–12. https://doi.org/10.1016/j.biomaterials.2017.09.00310.1016/j.biomaterials.2017.09.003 ↗
60. Shi JJ, Kantoff PW, Wooster R, Farokhzad OC (2017) Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 17(1):20–37. https://doi.org/10.1038/nrc.2016.10810.1038/nrc.2016.108 ↗
61. Shim MK, Park J, Yoon HY, Lee S, Um W, Kim JH, Kang SW, Seo JW, Hyun SW, Park JH, Byun Y, Kwon IC, Kim K (2019) Carrier-free nanoparticles of cathepsin B-cleavable peptide-conjugated doxorubicin prodrug for cancer targeting therapy. J Control Release 294:376–389. https://doi.org/10.1016/j.jconrel.2018.11.03210.1016/j.jconrel.2018.11.032 ↗
62. Thambi T, Park JH, Lee DS (2016) Hypoxia-responsive nanocarriers for cancer imaging and therapy: recent approaches and future perspectives. Chem Commun 52(55):8492–8500. https://doi.org/10.1039/c6cc02972h10.1039/c6cc02972h ↗
63. Torchilin V (2011) Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev 63(3):131–135. https://doi.org/10.1016/j.addr.2010.03.01110.1016/j.addr.2010.03.011 ↗
64. Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8(7):579–591. https://doi.org/10.1038/nrd280310.1038/nrd2803 ↗
65. Tubbs JL, Pegg AE, Tainer JA (2007) DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O-6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy. DNA Repair 6(8):1100–1115. https://doi.org/10.1016/j.dnarep.2007.03.01110.1016/j.dnarep.2007.03.011 ↗
66. Wang Y, Hu W, Ding B, Chen D, Cheng L (2020) cRGD mediated redox and pH dual responsive poly(amidoamine) dendrimer-poly(ethylene glycol) conjugates for efficiently intracellular antitumor drug delivery. Colloids Surfaces B Biointerfaces 194. https://doi.org/10.1016/j.colsurfb.2020.11119510.1016/j.colsurfb.2020.111195 ↗
67. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJH (2013) Strategies to address low drug solubility in discovery and development. Pharmacol Rev 65(1):315–499. https://doi.org/10.1124/pr.112.00566010.1124/pr.112.005660 ↗
68. Xie JJ, Fan ZX, Li Y, Zhang YY, Yu F, Su GH, Xie LY, Hou ZQ (2018) Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy. Int J Nanomedicine 13:1381–1398. https://doi.org/10.2147/ijn.S15231210.2147/ijn.S152312 ↗
69. Xie XD, Zhang XM, Chen J, Tang X, Wang MQ, Zhang L, Guo Z, Shen WR (2019) Fe3O4-solamargine induces apoptosis and inhibits metastasis of pancreatic cancer cells. Int J Oncol 54(3):905–915. https://doi.org/10.3892/ijo.2018.463710.3892/ijo.2018.4637 ↗
70. Xu KH, Wang F, Pan XH, Liu RP, Ma J, Kong FP, Tang B (2013) High selectivity imaging of nitroreductase using a near-infrared fluorescence probe in hypoxic tumor. Chem Commun 49(25):2554–2556. https://doi.org/10.1039/c3cc38980d10.1039/c3cc38980d ↗
71. Zeng Y, Ma JW, Zhan YH, Xu XY, Zeng Q, Liang JM, Chen XL (2018) Hypoxia-activated prodrugs and redox-responsive nanocarriers. Int J Nanomedicine 13:6551–6574. https://doi.org/10.2147/ijn.S17343110.2147/ijn.S173431 ↗
72. Zhang ZT, Huang-Fu MY, Xu WH, Han M (2019) Stimulus-responsive nanoscale delivery systems triggered by the enzymes in the tumor microenvironment. Eur J Pharm Biopharm 137:122–130. https://doi.org/10.1016/j.ejpb.2019.02.00910.1016/j.ejpb.2019.02.009 ↗
73. Zheng YH, You XR, Guan SY, Huang J, Wang LY, Zhang JY, Wu J (2019) Poly(Ferulic acid) with an anticancer effect as a drug nanocarrier for enhanced colon cancer therapy. Adv Funct Mater 29(15):1808646. https://doi.org/10.1002/adfm.20180864610.1002/adfm.201808646 ↗
74. Zhu R, Baumann RP, Penketh PG, Shyam K, Sartorelli AC (2013) Hypoxia-selective O-6-alkylguanine-DNA alkyltransferase inhibitors: design, synthesis, and evaluation of 6-(Benzyloxy)-2-(aryldiazenyl)-9H-purines as prodrugs of O-6-benzylguanine. J Med Chem 56(3):1355–1359. https://doi.org/10.1021/jm301804p10.1021/jm301804p ↗
75. Zong LL, Wang YL, Qiao P, Yu KK, Hou XQ, Wang PR, Zhang ZK, Pang XB, Pu XH, Yuan Q (2020) Reduction-sensitive poly(ethylene glycol)-polypeptide conjugate micelles for highly efficient intracellular delivery and enhanced antitumor efficacy of hydroxycamptothecin. Nanotechnology 31(16):165102. https://doi.org/10.1088/1361-6528/ab674910.1088/1361-6528/ab6749 ↗