Citation: Mengjie Ye, Yuan Gao, Mengyun Liang, Wei Qiu, Xianbin Ma, Jiming Xu, Junfeng Hu, Peng Xue, Yuejun Kang, Zhigang Xu. Microenvironment-responsive chemotherapeutic nanogels for enhancing tumor therapy via DNA damage and glutathione consumption[J]. Chinese Chemical Letters, ;2022, 33(9): 4197-4202. doi: 10.1016/j.cclet.2022.01.086 shu

Microenvironment-responsive chemotherapeutic nanogels for enhancing tumor therapy via DNA damage and glutathione consumption

Mengjie Ye ^a ,
Yuan Gao ^a ,
Mengyun Liang ^a ,
Wei Qiu ^a ,
Xianbin Ma ^a ,
Jiming Xu ^a ,
Junfeng Hu ^a ,
Peng Xue ^a ,
Yuejun Kang ^a ,
Zhigang Xu ^{a, b, *,}

a.
Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Materials and Energy and Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing 400715, China
b.
Key Laboratory of Laser Technology and Optoelectronic Functional Materials of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China

zgxu@swu.edu.cn

Received Date: 15 September 2021
Revised Date: 27 January 2022
Accepted Date: 28 January 2022
Available Online: 4 February 2022

Figures(4)

Although targeted therapy and immunotherapy are now shining in the treatment of some cancers, chemotherapy is still the cornerstone of drug treatment for many cancer patients. The emergence of chemotherapy prodrugs can improve the drug activity and reduce the side effects of chemotherapy. When used, the tumor microenvironment has characteristics different from normal tissues, and the existence of the microenvironment provided a more convenient way to design responsive nanodrugs. Herein, we designed a glutathione (GSH)-responsive prodrug nanogels for enhancing tumor chemotherapy. In the nanogels of HHNP, 10-hydroxycamptothecin (HCPT) played an essential role in killing cancer cells. HCPT was jointed with a cross-linker agent with disulfide bond and was further coated with polyethylene glycol, which not only prolonged the half-life of the drug, but also made HCPT accurate transport to the tumor fractions and achieved precise and controllable release. The proposal of HHNP effectively retained the biological activity of the drug, and introduced functions such as targeting, selective release and biodegradation, which greatly improved the medical efficiency of the drug and effectively reduced the toxic and side effects. This chemotherapeutic prodrug nanogel offers a new window for constructing efficient drug delivery platform.
- Nanogel,
- Prodrug,
- GSH-responsive,
- DNA damage,
- Chemotherapy
1. [1]
  S. Quader, K. Kataoka, Mol. Ther. 25 (2017) 1501–1513. doi: 10.1016/j.ymthe.2017.04.026
2. [2]
  K. Cheng, M. Sano, C.H. Jenkins, et al., ACS Nano 12 (2018) 4946–4958. doi: 10.1021/acsnano.8b02038
3. [3]
  S. Goel, D. Ni, W.B. Cai, et al., ACS Nano 11 (2017) 5233–5237. doi: 10.1021/acsnano.7b03675
4. [4]
  M.A. Knoll, R. Jagsi, K. Rosenzweig, JAMA Oncol. 5 (2019) 442. doi: 10.1001/jamaoncol.2018.5868
5. [5]
  K. Li, C.C. Lin, Y. He, et al., ACS Nano 14 (2020) 14164–14180. doi: 10.1021/acsnano.0c07071
6. [6]
  S. Bai, L.L. Yang, Y.J. Wang, et al., Small 16 (2020) 2000214. doi: 10.1002/smll.202000214
7. [7]
  W. Ma, Q. Chen, W. Xu, et al., Nano Res. 14 (2020) 846–857. doi: 10.1109/ei250167.2020.9347325
8. [8]
  G. Chen, Y. Yang, Q. Xu, et al., Nano Lett. 20 (2020) 8141–8150. doi: 10.1021/acs.nanolett.0c03127
9. [9]
  M. He, L. Yu, Y. Yang, et al., Chin. Chem. Lett. 31 (2020) 3178–3182. doi: 10.1016/j.cclet.2020.05.034
10. [10]
  L. Yu, Z. Wang, Z. Mo, et al., Acta Pharm. Sin. B 11 (2021) 2004–2015. doi: 10.1016/j.apsb.2021.02.001
11. [11]
  Y.Y. Yang, X. Liu, W. Ma, et al., Biomaterials 265 (2021) 120456. doi: 10.1016/j.biomaterials.2020.120456
12. [12]
  F. Ding, X.H. Gao, X.G. Huang, et al., Biomaterials 245 (2020) 119976. doi: 10.1016/j.biomaterials.2020.119976
13. [13]
  W. Tao, J.Q. Wang, W.J. Parak, et al., ACS Nano 13 (2019) 4876–4882. doi: 10.1021/acsnano.9b01696
14. [14]
  Q.W. Tian, Y.P. Li, S.S. Jiang, et al., Small 15 (2019) 1902926. doi: 10.1002/smll.201902926
15. [15]
  W. Wu, L. Luo, Y. Wang, et al., Theranostics 8 (2018) 3038–3058. doi: 10.7150/thno.23459
16. [16]
  S.L. Li, P.E. Saw, C.H. Lin, et al., Biomaterials 234 (2020) 119760. doi: 10.1016/j.biomaterials.2020.119760
17. [17]
  B. Fejerskov, M.T.J. Olesen, A.N. Zelikin, Adv. Drug Deliv. Rev. 118 (2017) 24–34. doi: 10.1016/j.addr.2017.04.013
18. [18]
  R. Mooney, A.A. Majid, J. Batalla, et al., Adv. Drug Deliv. Rev. 118 (2017) 35–51. doi: 10.1016/j.addr.2017.09.003
19. [19]
  W.B. Hu, P.N. Prasad, W. Huang, Acc. Chem. Res. 54 (2021) 697–706. doi: 10.1021/acs.accounts.0c00688
20. [20]
  C.N. Xu, Y.B. Wang, E.L. Wang, et al., Adv. Funct. Mater. 31 (2020) 2009314.
21. [21]
  H. Zhao, J.B. Xua, J.S. Wan, et al., Nano Today 36 (2021) 101058. doi: 10.1016/j.nantod.2020.101058
22. [22]
  G. Canavese, A. Ancona, L. Racca, et al., Chem. Eng. J. 340 (2018) 155–172. doi: 10.1016/j.cej.2018.01.060
23. [23]
  Y. Yoon, W. Tang, X.Y. Chen, Small Methods 1 (2017) 1700173. doi: 10.1002/smtd.201700173
24. [24]
  Y.E. Gao, S.X. Hou, J.Q. Cheng, et al., ACS Sustain. Chem. Eng. 9 (2021) 3213–3222. doi: 10.1021/acssuschemeng.0c08326
25. [25]
  S.X. Hou, Y.E. Gao, X.B. Ma, et al., Chem. Eng. J. 416 (2021) 129037. doi: 10.1016/j.cej.2021.129037
26. [26]
  D. Jia, X.B. Ma, Y. Lu, et al., Chin. Chem. Lett. 32 (2021) 162–167. doi: 10.1016/j.cclet.2020.11.052
27. [27]
  H. Guo, F.P. Li, W.G. Xu, et al., Adv. Sci. 5 (2018) 1800004. doi: 10.1002/advs.201800004
28. [28]
  K. Zhang, Y. Zhang, X. Meng, et al., Biomaterials 185 (2018) 301–309. doi: 10.1016/j.biomaterials.2018.09.033
29. [29]
  L. Feng, M. Gao, D. Tao, et al., Adv. Funct. Mater. 26 (2016) 2207–2217. doi: 10.1002/adfm.201504899
30. [30]
  B. Cao, F. Xiao, D. Xing, et al., Small 14 (2018) 1802008. doi: 10.1002/smll.201802008
31. [31]
  P. Zheng, Y. Liu, J. Chen, et al., Chin. Chem. Lett. 31 (2020) 1178–1182. doi: 10.1016/j.cclet.2019.12.001
32. [32]
  H. Huang, L. Mao, Z.H. Li, et al., J. Bioresour. Bioprod. 4 (2019) 231–241.
33. [33]
  X. Hu, S. Zhai, G. Liu, et al., Adv. Mater. 30 (2018) 1706307. doi: 10.1002/adma.201706307
34. [34]
  M. Jiang, J. Mu, O. Jacobson, et al., ACS Nano 14 (2020) 16875–16886. doi: 10.1021/acsnano.0c05722
35. [35]
  W. Shen, W. Liu, H. Yang, et al., Biomaterials 178 (2018) 706–719. doi: 10.1016/j.biomaterials.2018.02.011
36. [36]
  J.N. Li, W.G. Xu, D. Li, et al., ACS Nano 12 (2018) 6685–6699. doi: 10.1021/acsnano.8b01729
37. [37]
  L.J. Zhang, X. Zhang, G.H. Lu, et al., Small 15 (2019) 1805544. doi: 10.1002/smll.201805544
38. [38]
  W. Jiang, Q. Li, L. Xiao, et al., ACS Nano 12 (2018) 5684–5698. doi: 10.1021/acsnano.8b01508
39. [39]
  K. Duskova, P. Lejault, É. . Benchimol, et al., J. Am. Chem. Soc. 142 (2020) 424–435. doi: 10.1021/jacs.9b11150
40. [40]
  U.S. Srinivas, B. Tan, B.A. Vellayappan, et al., Redox Biology 25 (2019) 101084. doi: 10.1016/j.redox.2018.101084
41. [41]
  G. Barouti, C.G. Jaffredo, S.M. Guillaume, Prog. Polym. Sci. 73 (2017) 1–31. doi: 10.1016/j.progpolymsci.2017.05.002
42. [42]
  W.W. Mu, Q.H. Chu, Y.J. Liu, et al., Nano-micro Lett. 12 (2020) 142. doi: 10.1007/s40820-020-00482-6
43. [43]
  J.S. Lan, L. Liu, R.F. Zeng, et al., Chem. Eng. J. 407 (2021) 127212. doi: 10.1016/j.cej.2020.127212
44. [44]
  X.Y. Zhong, X.W. Wang, L. Cheng, et al., Adv. Funct. Mater. 30 (2019) 1907954.
45. [45]
  Y. Lu, D. Jia, X.B. Ma, et al., ACS Appl. Mater. Interfaces 13 (2021) 8940–8951. doi: 10.1021/acsami.0c21710
46. [46]
  X.B. Ma, S.C. Yang, T. Zhang, et al., Acta Pharm. Sin. B 12 (2022) 451–466. doi: 10.1016/j.apsb.2021.05.016
47. [47]
  Y.J. Wang, M.H. Zu, X.B. Ma, et al., ACS Appl. Mater. Interfaces 12 (2020) 50896–50908. doi: 10.1021/acsami.0c15781
48. [48]
  H.G. Xiong, X.B. Ma, X.L. Wang, et al., Adv. Funct. Mater. 31 (2021) 2100007. doi: 10.1002/adfm.202100007
49. [49]
  R. Liu, M.N. Yu, X.T. Yang, et al., Adv. Funct. Mater. 29 (2019) 1808462. doi: 10.1002/adfm.201808462
50. [50]
  S. Wang, P. Huang, X.Y. Chen, Adv. Mater. 28 (2016) 7340–7364. doi: 10.1002/adma.201601498
51. [51]
  P. Zheng, Y. Liu, J.X. Ding, et al., Chin. Chem. Lett. 31 (2020) 1178–1182. doi: 10.1016/j.cclet.2019.12.001
52. [52]
  X.X. Shi, Y. Zhang, Y. Tian, et al., Small Methods 5 (2020) 2000416. doi: 10.1002/smtd.202000416
53. [53]
  Q.W. Zhu, M. Saeed, H.J. Yu, et al., Chin. Chem. Lett. 31 (2020) 1051–1059. doi: 10.1016/j.cclet.2019.12.002
1. [1]
  Tianxu Zhang , Dexuan Xiao , Mi Zhou , Yunfeng Lin , Tao Zhang , Xiaoxiao Cai . Protective effect of osteogenic growth peptide functionalized tetrahedral DNA nanostructure on bone marrow and bone formation ability in chemotherapy-induced myelosuppressive mice. Chinese Chemical Letters, 2025, 36(8): 110594-. doi: 10.1016/j.cclet.2024.110594
2. [2]
  Haotian Shi , Yuchao Luo , Song Zhang , Meijun Zhao , Chaoyong Liu , Qing Pei , Helei Wang , Qiong Dai , Zhigang Xie , Bin Xu , Wenjing Tian . Dual-responsive nanogels with high drug loading for enhanced tumor targeting and treatment. Chinese Chemical Letters, 2025, 36(10): 110775-. doi: 10.1016/j.cclet.2024.110775
3. [3]
  Yunkang Tong , Haiqiao Huang , Haolan Li , Mingle Li , Wen Sun , Jianjun Du , Jiangli Fan , Lei Wang , Bin Liu , Xiaoqiang Chen , Xiaojun Peng . Cooperative bond scission by HRP/H₂O₂ for targeted prodrug activation. Chinese Chemical Letters, 2024, 35(12): 109663-. doi: 10.1016/j.cclet.2024.109663
4. [4]
  Wenbin Zhou , Yafei Gao , Xinyu Feng , Yanqing Zhang , Cong Yang , Lanxi He , Fenghe Zhang , Xiaoguang Li , Qing Li . Biomimetic nanoplatform integrates FRET-enhanced photodynamic therapy and chemotherapy for cascaded revitalization of the tumor immune microenvironment in OSCC. Chinese Chemical Letters, 2025, 36(1): 109763-. doi: 10.1016/j.cclet.2024.109763
5. [5]
  Cheng-Zhe Gao , Hao-Ran Jia , Tian-Yu Wang , Xiao-Yu Zhu , Xiaofeng Han , Fu-Gen Wu . A dual drug-loaded tumor vasculature-targeting liposome for tumor vasculature disruption and hypoxia-enhanced chemotherapy. Chinese Chemical Letters, 2025, 36(1): 109840-. doi: 10.1016/j.cclet.2024.109840
6. [6]
  Tingting Hu , Chao Shen , Xueyan Wang , Fengbo Wu , Zhiyao He . Tumor microenvironment-sensitive polymeric nanoparticles for synergetic chemo-photo therapy. Chinese Chemical Letters, 2024, 35(11): 109562-. doi: 10.1016/j.cclet.2024.109562
7. [7]
  Chuyu Huang , Zhishan Liu , Linping Zhao , Zuxiao Chen , Rongrong Zheng , Xiaona Rao , Yuxuan Wei , Xin Chen , Shiying Li . Metal-coordinated oxidative stress amplifier to suppress tumor growth combined with M2 macrophage elimination. Chinese Chemical Letters, 2024, 35(12): 109696-. doi: 10.1016/j.cclet.2024.109696
8. [8]
  Zhi Li , Shuya Pan , Yuan Tian , Shaowei Liu , Weifeng Wei , Jinlin Wang , Tianfeng Chen , Ling Wang . Selenium nanoparticles enhance the chemotherapeutic efficacy of pemetrexed against non-small cell lung cancer. Chinese Chemical Letters, 2024, 35(12): 110018-. doi: 10.1016/j.cclet.2024.110018
9. [9]
  Du Liu , Yuyan Li , Hankun Zhang , Benhua Wang , Chaoyi Yao , Minhuan Lan , Zhanhong Yang , Xiangzhi Song . Three-in-one erlotinib-modified NIR photosensitizer for fluorescence imaging and synergistic chemo-photodynamic therapy. Chinese Chemical Letters, 2025, 36(2): 109910-. doi: 10.1016/j.cclet.2024.109910
10. [10]
  Lintao Wu , Yujia Meng , Xumei Zheng , Yiqiao Bai , Chun Han , Zhijun Wang , Jie Yang , Xiaobi Jing , Yong Yao . Pillar[5]arene based prodrug as a GSH-responsive SO₂ nanogenerator for effective gas cancer therapy. Chinese Chemical Letters, 2025, 36(9): 110808-. doi: 10.1016/j.cclet.2024.110808
11. [11]
  Lin Li , Bingjun Sun , Jin Sun , Lin Chen , Zhonggui He . Binary prodrug nanoassemblies combining chemotherapy and ferroptosis activation for efficient triple-negative breast cancer therapy. Chinese Chemical Letters, 2024, 35(10): 109538-. doi: 10.1016/j.cclet.2024.109538
12. [12]
  Tengjiao Wang , Tian Cheng , Rongjun Liu , Zeyi Wang , Yuxuan Qiao , An Wang , Peng Li . Conductive Hydrogel-based Flexible Electronic System: Innovative Experimental Design in Flexible Electronics. University Chemistry, 2024, 39(4): 286-295. doi: 10.3866/PKU.DXHX202309094
13. [13]
  Shupeng Han , Caiting Deng , Meichen Zheng , Linwei Yang , Hancun Kong , Yongchao He , Yinuo Zheng , Guowei Deng , Yu Ren , Feifei An . A GSH-responsive NIR-BODIPY fluorophore with large Stokes-shift for tumor specific fluorescence imaging and surgical guidance. Chinese Chemical Letters, 2025, 36(7): 110459-. doi: 10.1016/j.cclet.2024.110459
14. [14]
  Jinyu Guo , Yandai Lin , Shaohua He , Yueqing Chen , Fenglu Li , Renjie Ruan , Gaoxing Pan , Hexin Nan , Jibin Song , Jin Zhang . Utilizing dual-responsive iridium(Ⅲ) complex for hepatocellular carcinoma: Integrating photoacoustic imaging with chemotherapy and photodynamic therapy. Chinese Chemical Letters, 2024, 35(9): 109537-. doi: 10.1016/j.cclet.2024.109537
15. [15]
  Li Fu , Ziye Su , Shuyang Wu , Yanfen Cheng , Chuan Hu , Jinming Zhang . Redox-responsive hyaluronic acid-celastrol prodrug micelles with glycyrrhetinic acid co-delivery for tumor combination therapy. Chinese Chemical Letters, 2025, 36(5): 110227-. doi: 10.1016/j.cclet.2024.110227
16. [16]
  Yong-Dan Zhao , Yidan Wang , Rongrong Wang , Lina Chen , Hengtong Zuo , Xi Wang , Jihong Qiang , Geng Wang , Qingxia Li , Canqi Ping , Shuqiu Zhang , Hao Wang . Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH. Chinese Chemical Letters, 2024, 35(6): 108929-. doi: 10.1016/j.cclet.2023.108929
17. [17]
  Di ZHANG , Tianxiang XIE , Xu HE , Wanyu WEI , Qi FAN , Jie QIAO , Gang JIN , Ningbo LI . Construction and antitumor activity of pH/GSH dual-responsive magnetic nanodrug. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 786-796. doi: 10.11862/CJIC.20240329
18. [18]
  Xinran Xi , Xiyu Wang , Ziyue Xi , Chuanyong Fan , Yingying Jiang , Zhenhua Li , Lu Xu . Facile GSH responsive glycyrrhetinic acid conjunction for liver targeting therapy. Chinese Chemical Letters, 2025, 36(10): 110773-. doi: 10.1016/j.cclet.2024.110773
19. [19]
  Yuanzheng Wang , Chen Zhang , Shuyan Han , Xiaoli Kong , Changyun Quan , Jun Wu , Wei Zhang . Cancer cell membrane camouflaged biomimetic gelatin-based nanogel for tumor inhibition. Chinese Chemical Letters, 2024, 35(11): 109578-. doi: 10.1016/j.cclet.2024.109578
20. [20]
  Huipeng Li , Xue Yang , Minjie Sun . Self-strengthened cascade-explosive nanogel using host-guest interaction strategy for synergistic tumor treatment. Chinese Chemical Letters, 2025, 36(8): 110651-. doi: 10.1016/j.cclet.2024.110651

Get Citation

PDF

XML

Metrics

PDF Downloads(6)
Abstract views(1845)
HTML views(69)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142