Citation: Ronghua Jin, Zhongning Liu, Tao Liu, Pingyun Yuan, Yongkang Bai, Xin Chen. Redox-responsive micelles integrating catalytic nanomedicine and selective chemotherapy for effective tumor treatment[J]. Chinese Chemical Letters, ;2021, 32(10): 3076-3082. doi: 10.1016/j.cclet.2021.03.084 shu

Redox-responsive micelles integrating catalytic nanomedicine and selective chemotherapy for effective tumor treatment

Ronghua Jin ^{a, c} ,
Zhongning Liu ^b ,
Tao Liu ^a ,
Pingyun Yuan ^a ,
Yongkang Bai ^a ,
Xin Chen ^{a, *,}

a.
School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi'an Jiao Tong University, Xi'an 710049, China
b.
Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
c.
Pharmaceutical College, Guangxi Medical University, Nanning 530021, China

chenx2015@xjtu.edu.cn

Received Date: 23 January 2021
Revised Date: 31 March 2021
Accepted Date: 1 April 2021
Available Online: 2 April 2021

Figures(5)

Chemotherapy is one of the most conventional modalities for cancer therapy. However, the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy. Considering the ability of nitric oxide (NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance, a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the chemotherapy. Herein, a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin (DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor treatment. The micelle consists of DOX as core, arginine/glucose oxidase (Arg/GOx) as shell and redox-responsive disulfide bond as a linker, which is denoted as micelle-DOX-Arg-GOx. The Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide (H₂O₂) for increasing the generation of NO. Moreover, the glucose supply could be simultaneously blocked by the catalytic process, which further enhanced therapeutic efficiency. This micelle requests a tumor-specific microenvironment (a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy, starvation therapy (catalytic medicine), and gas therapy for tumor treatment, which resulted in significant cytotoxicity to tumor tissue.
- Chemotherapy,
- Gas therapy,
- Starvation therapy,
- Carrier-free,
- Tumor treatment
1. [1]
  X. Ding, F. Zhu, S. Gao, Food Chem. 131 (2012) 677-684 doi: 10.1016/j.foodchem.2011.09.060
2. [2]
  J. Zhou, G. Yu, F. Huang, Chem. Soc. Rev. 46 (2017) 7021-7053 doi: 10.1039/C6CS00898D
3. [3]
  J. Wen, K. Yang, F. Liu, et al., Chem. Soc. Rev. 46 (2017) 6024-6045 doi: 10.1039/C7CS00219J
4. [4]
  V.P. Torchilin, Nat. Rev. Drug. Discov. 13 (2014) 813-827 doi: 10.1038/nrd4333
5. [5]
  R. Jin, J. Xie, X. Yang, et al., Biomater. Sci. 8 (2020) 1865-1874 doi: 10.1039/c9bm01992h
6. [6]
  Y. Lu, A.A. Aimetti, R. Langer, Z. Gu, Nat. Rev. Mater. 2 (2016) 16075
7. [7]
  Y. Cui, R. Deng, X. Li, et al., Chin. Chem. Lett. 30 (2019) 2291-2294 doi: 10.1016/j.cclet.2019.08.017
8. [8]
  L. Kong, Q. Chen, F. Campbell, et al., Adv. Healthc. Mater. 9 (2020) e1901489 doi: 10.1002/adhm.201901489
9. [9]
  R. Jin, Z. Liu, Y. Bai, et al., ACS Omega 3 (2018) 4306-4315 doi: 10.1021/acsomega.8b00427
10. [10]
  R. Jin, Z. Liu, Y. Bai, et al., Adv. Funct. Mater. 28 (2018) 1801961 doi: 10.1002/adfm.201801961
11. [11]
  R. Jin, Z. Liu, Y. Bai, et al., ACS Appl. Nano Mater. 1 (2018) 302-309 doi: 10.1021/acsanm.7b00152
12. [12]
  R. Cao, W. Sun, Z. Zhang, et al., Chin. Chem. Lett. 31 (2020) 3127-3130 doi: 10.1016/j.cclet.2020.06.031
13. [13]
  A. Zhang, L. Hai, T. Wang, et al., Chin. Chem. Lett. 31 (2020) 3158-3162 doi: 10.1016/j.cclet.2020.04.035
14. [14]
  L. Chen, Z. Liu, R. Jin, et al., J. Mater. Chem. B 6 (2018) 6262-6268 doi: 10.1039/c8tb01182f
15. [15]
  Y. Song, D. Li, J. He, et al., Chin. Chem. Lett. 30 (2019) 2027-2031 doi: 10.1016/j.cclet.2019.04.052
16. [16]
  T. Liu, Z. Liu, J. Chen, et al., J. Biomed. Nanotechnol 14 (2018) 1107-1116 doi: 10.1166/jbn.2018.2573
17. [17]
  J. Hu, Y. Xu, Y. Zhang, Chin. Chem. Lett. 30 (2019) 2039-2042 doi: 10.1016/j.cclet.2019.05.017
18. [18]
  X. Jia, Y. Zhang, Y. Zou, et al., Adv. Mater. 30 (2018) e1704490 doi: 10.1002/adma.201704490
19. [19]
  X. Hu, Z. Chai, L. Lu, et al., Adv. Funct. Mater. 29 (2019) 1807941 doi: 10.1002/adfm.201807941
20. [20]
  X. Chen, A.H. Soeriyadi, X. Lu, et al., Adv. Funct. Mater. 24 (2014) 6999-7006 doi: 10.1002/adfm.201402339
21. [21]
  R. Jin, Q. Wang, G. Dou, et al., Appl. Mater. Today 21 (2020) 100883 doi: 10.1016/j.apmt.2020.100883
22. [22]
  I. Gjuroski, E. Girousi, C. Meyer, et al., J. Control. Release 316 (2019) 150-167 doi: 10.1016/j.jconrel.2019.10.010
23. [23]
  Y. Dong, D.J. Siegwart, D.G. Anderson, Adv. Drug. Deliv. Rev. 144 (2019) 133-147 doi: 10.1016/j.addr.2019.05.004
24. [24]
  F. Tosi, M.C.A. Stuart, S.J. Wezenberg, B.L. Feringa, Angew. Chem. Int. Ed. 58 (2019) 14935-14939 doi: 10.1002/anie.201908010
25. [25]
  W. Fan, N. Lu, P. Huang, et al., Angew. Chem. Int. Ed. 56 (2017) 1229-1233 doi: 10.1002/anie.201610682
26. [26]
  W. Fan, B.C. Yung, X. Chen, Angew. Chem. Int. Ed. 57 (2018) 8383-8394 doi: 10.1002/anie.201800594
27. [27]
  M.F. Chung, H.Y. Liu, K.J. Lin, et al., Angew. Chem. Int. Ed. 54 (2015) 9890-9893 doi: 10.1002/anie.201504444
28. [28]
  R. Guo, Y. Tian, Y. Wang, W. Yang, Adv. Funct. Mater. 27 (2017) 1606398 doi: 10.1002/adfm.201606398
29. [29]
  K. Zhang, H. Xu, X. Jia, et al., ACS Nano 10 (2016) 10816-10828 doi: 10.1021/acsnano.6b04921
30. [30]
  W. Fan, N. Lu, P. Huang, et al., Angew. Chem. Int. Ed. 56 (2017) 1229-1233 doi: 10.1002/anie.201610682
31. [31]
  J. An, Y.G. Hu, C. Li, et al., Biomaterials 230 (2020) 119636 doi: 10.1016/j.biomaterials.2019.119636
32. [32]
  S. Kudo, Y. Nagasaki, J. Control. Release 217 (2015) 256-262 doi: 10.1016/j.jconrel.2015.09.019
33. [33]
  Z. Yuan, C. Lin, Y. He, et al., ACS Nano 14 (2020) 3546-3562 doi: 10.1021/acsnano.9b09871
34. [34]
  W. Fan, W. Bu, Z. Zhang, et al., Angew. Chem. Int. Ed. 54 (2015) 14026-14030 doi: 10.1002/anie.201504536
35. [35]
  M. Huo, L. Wang, Y. Chen, J. Shi, Nat. Commun. 8 (2017) 357 doi: 10.1038/s41467-017-00424-8
36. [36]
  W. Zhao, J. Hu, W. Gao, ACS Appl. Mater. Interfaces 9 (2017) 23528-23535 doi: 10.1021/acsami.7b06814
37. [37]
  P.D.W. Eckford, F.J. Sharom, Chem. Rev. 109 (2009) 2989-3011 doi: 10.1021/cr9000226
38. [38]
  G. Minotti, P. Menna, E. Salvatorelli, et al., Pharmacol. Rev. 56 (2004) 185-229 doi: 10.1124/pr.56.2.6
1. [1]
  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
2. [2]
  Ji Liu , Dongsheng He , Tianjiao Hao , Yumin Hu , Yan Zhao , Zhen Li , Chang Liu , Daquan Chen , Qiyue Wang , Xiaofei Xin , Yan Shen . Gold mineralized "hybrid nanozyme bomb" for NIR-II triggered tumor effective permeation and cocktail therapy. Chinese Chemical Letters, 2024, 35(9): 109296-. doi: 10.1016/j.cclet.2023.109296
3. [3]
  Qiuxia Tan , E Pang , Qin Wang , Yuanyu Tang , Pan Zhu , Shaojing Zhao , Jianing Yi , Shiguang Jin , Minhuan Lan . Manganese carbonate-based nanoplatform for starvation therapy cascaded chemodynamic therapy, enhanced phototherapy and immune activation. Chinese Chemical Letters, 2025, 36(10): 110770-. doi: 10.1016/j.cclet.2024.110770
4. [4]
  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
5. [5]
  Wei Zhou , Di He , Ning Liu , Ying Li , Wenzhao Han , Weiping Zhou , Siyu Zhang , Cong Yu . A PDI-based NIR-Ⅱ fluorescence imaging guided molecular phototheranostic platform for GSH-triggered gas therapy, mild photothermal therapy and NIR-activated photodynamic therapy. Chinese Chemical Letters, 2025, 36(11): 110854-. doi: 10.1016/j.cclet.2025.110854
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]
  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
8. [8]
  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
9. [9]
  Yingtao Zhong , Ziwen Qiu , Yanmei Li , Jiaqi Huang , Zhenming Lu , Renjiang Kong , Ni Yan , Hong Cheng . Nutrients deprivation of biomimetic nanozymes for cascade catalysis triggered and oxidative damage induced tumor eradication. Chinese Chemical Letters, 2025, 36(3): 109846-. doi: 10.1016/j.cclet.2024.109846
10. [10]
  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
11. [11]
  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
12. [12]
  Jing Zhang , Charles Wang , Yaoyao Zhang , Haining Xia , Yujuan Wang , Kun Ma , Junfeng Wang . Application of magnetotactic bacteria as engineering microrobots: Higher delivery efficiency of antitumor medicine. Chinese Chemical Letters, 2024, 35(10): 109420-. doi: 10.1016/j.cclet.2023.109420
13. [13]
  Bairui Zeng , Zhixiang Mu , Tianxi Shen , Xiaoliang Qi , Yuanqi Chen , Kezheng Lei , Chen Huang , Yi Wang , Rongdang Hu , Xiaojun Cai , Jianliang Shen , Hui Deng . A self-propelled nanovesicle with robust antibacterial and regeneration-promoting capabilities for treating biofilm-induced periodontitis. Chinese Chemical Letters, 2025, 36(6): 110350-. doi: 10.1016/j.cclet.2024.110350
14. [14]
  Xiaoyi Meng , Xinyue Sun , Zhaogang Sun , Yue Cheng , Yong Wang , Jun Ye , Yin Xiao , Hongqian Chu . Supramolecular-orchestrated carrier-free chemodynamic synergists with augmented oxidative damage for potentiated cancer therapy. Chinese Chemical Letters, 2025, 36(5): 110765-. doi: 10.1016/j.cclet.2024.110765
15. [15]
  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
16. [16]
  Hanyong Wang , Weijia Zhang , Chenlu Huang , Xinyu Yang , Qingyu Yu , Hai Wang , Wen Li , Linhua Zhang , Dunwan Zhu . Personalized tumor vaccines based on carrier-free double-adjuvant nanoparticles and tumor-associated antigens for enhancing immune responses. Chinese Chemical Letters, 2025, 36(7): 111092-. doi: 10.1016/j.cclet.2025.111092
17. [17]
  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
18. [18]
  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
19. [19]
  Yang Liu , Minglu Li , Jianxun Ding , Xuesi Chen . Glycoengineering-assistant biomineralization for tumor blockade therapy. Chinese Chemical Letters, 2025, 36(5): 110146-. doi: 10.1016/j.cclet.2024.110146
20. [20]
  Lijuan Liu , Zhihao Zhao , Feiwan Zou , Wukun Liu , Yunlong Lu . Advances in combination therapy for the treatment of estrogen receptor positive breast cancer. Chinese Chemical Letters, 2025, 36(10): 111451-. doi: 10.1016/j.cclet.2025.111451

Get Citation

PDF

XML

Metrics

PDF Downloads(5)
Abstract views(1313)
HTML views(46)

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