Tumor-Specific On-Site Activation of Cisplatin via Cascade Catalytic-Redox Reactions for Highly Efficient Chemo-Immunotherapy
Dr. Gang-Gang Yang
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
These authors contributed equally to this work.
Search for more papers by this authorBin Liu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006 P.R. China
These authors contributed equally to this work.
Search for more papers by this authorWei Liu
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
These authors contributed equally to this work.
Search for more papers by this authorLan Zhang
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
Search for more papers by this authorCan Ke
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
Search for more papers by this authorDr. Xinya Han
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
Search for more papers by this authorCorresponding Author
Dr. Qian Cao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006 P.R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Dr. Zong-Wan Mao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006 P.R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorDr. Gang-Gang Yang
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
These authors contributed equally to this work.
Search for more papers by this authorBin Liu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006 P.R. China
These authors contributed equally to this work.
Search for more papers by this authorWei Liu
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
These authors contributed equally to this work.
Search for more papers by this authorLan Zhang
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
Search for more papers by this authorCan Ke
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
Search for more papers by this authorDr. Xinya Han
School of Chemistry and Chemical Engineering Anhui University of Technology, Ma'anshan, Anhui, 243002 P.R. China
Search for more papers by this authorCorresponding Author
Dr. Qian Cao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006 P.R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Dr. Zong-Wan Mao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006 P.R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorGraphical Abstract
A double-lock protected PtII nanomedicine has been developed, which performs cascade unlocking of cisplatin (cDDP) via catalytic-redox reactions, thus achieving tumor-specific “on-site” activation of cDDP in the nucleus accompanied with substantial induction of ferroptosis for highly efficient chemo-immunotherapy.
Abstract
The therapeutic efficiency of platinum drugs is always limited by low utilization, side effects, and Pt-resistance. Herein, a double-lock protected PtII nanomedicine named PtNP@Cu has been developed, which performs cascade unlocking of dechlorinated cisplatin (DP) via catalytic-redox reactions, thus achieving tumor-specific “on-site” activation of cisplatin (cDDP) in the nucleus accompanied with substantial induction of ferroptosis of cancer cells. This design avoids the premature release of active PtII species in normal cells or in the cytoplasm of cancer cells before reaching nucleus, thereby ensuring maximum amplification of Pt-DNA crosslinking with tumor-specificity. Meanwhile, substantial GSH depletion and ROS production induced by cascade catalytic-redox reactions results in ferroptosis of cancer cells, which further reduces GSH-mediated cDDP detoxification, overcomes Pt-resistance, and enhances immunogenicity, ultimately realizing highly efficient tumor-specific chemotherapy and antitumor immunity in vivo. This work provides a new strategy for effectively and comprehensively addressing the issues of low utilization, side effects, and drug resistance problems of platinum drugs, which is also promising for chemo-immunotherapy.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supporting information of this article.
Supporting Information
| Filename | Description |
|---|---|
| anie202500996-sup-0001-SuppMat.pdf5.6 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Q. Peña, A. Wang, O. Zaremba, Y. Shi, H. W. Scheeren, J. M. Metselaar, F. Kiessling, R. M. Pallares, S. Wuttke, T. Lammers, Chem. Soc. Rev. 2022, 51, 2544–2582.
- 2X. Wang, Z. Guo, Chem. Soc. Rev. 2013, 42, 202–224.
- 3Y. Wang, L. Cai, H. Li, H. Chen, T. Yang, Y. Tan, Z. Guo, X. Wang, Angew. Chem. Int. Ed. 2023, 62, e202309043.
- 4X. Xue, C. Qian, H. Fang, H. K. Liu, H. Yuan, Z. Guo, Y. Bai, W. He, Angew. Chem. Int. Ed. 2019, 58, 12661–12666.
- 5K. Peng, B.-B. Liang, W. Liu, Z.-W. Mao, Coord. Chem. Rev. 2021, 449, 214210.
- 6M. A. Fuertes, C. Alonso, J. M. Pérez, Chem. Rev. 2003, 103, 645–662.
- 7S. Yuan, Y. Zhu, Y. Dai, Y. Wang, D. Jin, M. Liu, L. Tang, F. Arnesano, G. Natile, Y. Liu, Angew. Chem. Int. Ed. 2022, 61, e202114250.
- 8F. Gao, X. Yang, X. Luo, X. Xue, C. Qian, M. Sun, Adv. Funct. Mater. 2020, 30, 2001546.
- 9J. Chen, X. Wang, Y. Yuan, H. Chen, L. Zhang, H. Xiao, J. Chen, Y. Zhao, J. Chang, W. Guo, Sci. Adv. 2021, 7, eabc5267.
- 10H. Ge, J. Du, J. Zheng, N. Xu, Q. Yao, S. Long, J. Fan, X. Peng, Chem. Eng. J. 2022, 446, 137040.
- 11Z. Wang, Z. Xu, G. Zhu, Angew. Chem. Int. Ed. 2016, 55, 15564–15568.
- 12Y. Yang, Z. Mai, Y. Zhang, Z. Yu, W. Li, Y. Zhang, F. Li, P. Timashev, P. Luan, D. Luo, ACS Nano 2023, 17, 1275–1286.
- 13W. H. Ang, M. Myint, S. J. Lippard, J. Am. Chem. Soc. 2010, 132, 7429–7435.
- 14K. G. Z. Lee, M. V. Babak, A. Weiss, P. J. Dyson, P. Nowak-Sliwinska, D. Montagner, W. H. Ang, ChemMedChem 2018, 13, 1210–1217.
- 15J. Zhang, B. Zhao, S. Chen, Y. Wang, Y. Zhang, Y. Wang, D. Wei, L. Zhang, G. Rong, Y. Weng, ACS Nano 2020, 14, 14831–14845.
- 16G. Liang, T. Sadhukhan, S. Banerjee, D. Tang, H. Zhang, M. Cui, N. Montesdeoca, J. Karges, H. Xiao, Angew. Chem. Int. Ed. 2023, 62, e202301074.
- 17X. Zeng, Y. Wang, J. Han, W. Sun, H. J. Butt, X. J. Liang, S. Wu, Adv. Mater. 2020, 32, 2004766.
- 18L. Cao, H. Tian, M. Fang, Z. Xu, D. Tang, J. Chen, J. Yin, H. Xiao, K. Shang, H. Han, X. Li, Biomaterials 2022, 290, 121856.
- 19J. Cheng, L. Li, D. Jin, Y. Dai, Y. Zhu, J. Zou, M. Liu, W. Yu, J. Yu, Y. Sun, Adv. Mater. 2023, 35, 2210037.
- 20Y. Cong, H. Xiao, H. Xiong, Z. Wang, J. Ding, C. Li, X. Chen, X. J. Liang, D. Zhou, Y. Huang, Adv. Mater. 2018, 30, 1706220.
- 21K. Yang, G. Yu, Z. Yang, L. Yue, X. Zhang, C. Sun, J. Wei, L. Rao, X. Chen, R. Wang, Angew. Chem. Int. Ed. 2021, 60, 17570–17578.
- 22Y. Ma, Z. Su, L. Zhou, L. He, Z. Hou, J. Zou, Y. Cai, D. Chang, J. Xie, C. Zhu, Adv. Mater. 2022, 34, 2107560.
- 23Z. Zhou, P. Shi, C. Wang, Y. Sun, C. Gao, Coord. Chem. Rev. 2024, 508, 215774.
- 24A. M. Itoo, B. Ghosh, S. Biswas, Coord. Chem. Rev. 2024, 508, 215796.
- 25Y. Han, P. Wen, J. Li, K. Kataoka, J. Controlled Release 2022, 345, 709–720.
- 26D. Wei, J. Fan, J. Yan, C. Liu, J. Cao, C. Xu, Y. Sun, H. Xiao, J. Am. Chem. Soc. 2024, 146, 1185–1195.
- 27Z. Deng, N. Wang, Y. Liu, Z. Xu, Z. Wang, T.-C. Lau, G. Zhu, J. Am. Chem. Soc. 2020, 142, 7803–7812.
- 28B. Chiavarino, M. E. Crestoni, S. Fornarini, D. Scuderi, J.-Y. Salpin, Inorg. Chem. 2015, 54, 3513–3522.
- 29X. Zhang, Y. Cheng, J. You, J. Zhang, C. Yin, J. Zhang, Nat. Commun. 2022, 13, 1117.
- 30Y. Zhan, Y. Wang, M. Wang, X. Ding, X. Wang, Adv. Mater. Interfaces 2020, 7, 1901490.
- 31N. J. Patel, B. S. Bhatt, M. N. Patel, Inorg. Chim. Acta 2019, 498, 119130.
- 32S. Hadian Rasanani, M. E. Moghadam, E. Soleimani, A. Divsalar, D. Ajloo, A. Tarlani, M. Amiri, J. Biomol. Struct. Dyn. 2018, 36, 3058–3076.
- 33R. G. Mohamed, F. M. Elantabli, A. A. A. Aziz, H. Moustafa, S. M. El-Medani, J. Mol. Struct. 2019, 1176, 501–514.
- 34R. Dong, Y. Su, S. Yu, Y. Zhou, Y. Lu, X. Zhu, Chem. Commun. 2013, 49, 9845.
- 35S. K. Filippov, R. Khusnutdinov, A. Murmiliuk, W. Inam, L. Y. Zakharova, H. Zhang, V. V. Khutoryanskiy, Mater. Horiz. 2023, 10, 5354–5370.
- 36Z. Chen, R. K. Kankala, L. Long, S. Xie, A. Chen, L. Zou, Coord. Chem. Rev. 2023, 481, 215051.
- 37Y. Fan, D. Shen, Y. Yan, X. Hu, Y. Guo, Y. Zhong, Z. Li, L. Xie, J. Polym. Environ. 2022, 30, 4863–4876.
- 38B. Ma, S. Wang, F. Liu, S. Zhang, J. Duan, Z. Li, Y. Kong, Y. Sang, H. Liu, W. Bu, J. Am. Chem. Soc. 2019, 141, 849–857.
- 39K. Yang, S. Qi, X. Yu, B. Bai, X. Zhang, Z. Mao, F. Huang, G. Yu, Angew. Chem. Int. Ed. 2022, 134, e202203786.
- 40A. D. Bokare, W. Choi, J. Hazard. Mater. 2014, 275, 121–135.
- 41X. Kuang, Y. Liu, H. Luo, Q. Li, F. Wu, C. Fan, J. Liu, J. Am. Chem. Soc. 2023, 145, 26932–26946.
- 42S. Kasamatsu, S. Komae, K. Matsukura, Y. Kakihana, K. Uchida, H. Ihara, Antioxidants 2021, 10, 1434.
- 43M.-M. Wang, D.-P. Deng, A.-M. Zhou, Y. Su, Z.-H. Yu, H. K. Liu, Z. Su, Inorg. Chem. 2024, 63, 4758–4769.
- 44X. Xu, Z. Zeng, X. Ding, T. Shan, Q. Liu, M. Chen, J. Chen, M. Xia, Y. He, Z. Huang, Y. Huang, C. Zhao, Biomaterials 2021, 277, 121128.
- 45N. Gong, X. Ma, X. Ye, Q. Zhou, X. Chen, X. Tan, S. Yao, S. Huo, T. Zhang, S. Chen, Nat. Nanotechnol. 2019, 14, 379–387.
- 46H. Liu, L. Zhang, J. Chen, Y. Zhai, Y. Zeng, L. Li, Anal. Bioanal. Chem. 2013, 405, 9563–9570.
- 47X. Su, W. J. Wang, Q. Cao, H. Zhang, B. Liu, Y. Ling, X. Zhou, Z. W. Mao, Angew. Chem. Int. Ed. 2022, 61, e202115800.
- 48Z. Wang, N. Wang, S.-C. Cheng, K. Xu, Z. Deng, S. Chen, Z. Xu, K. Xie, M.-K. Tse, P. Shi, Chem 2019, 5, 3151–3165.
- 49S. Zhang, D. Song, W. Yu, J. Li, X. Wang, Y. Li, Z. Zhao, Q. Xue, J. Zhao, J. P. Li, Natl. Sci. Rev. 2024, 11, nwae020.
- 50W. J. Wang, Y. Y. Ling, Y. M. Zhong, Z. Y. Li, C. P. Tan, Z. W. Mao, Angew. Chem. Int. Ed. 2022, 61, e202115247.
- 51X. Meng, J. Deng, F. Liu, T. Guo, M. Liu, P. Dai, A. Fan, Z. Wang, Y. Zhao, Nano Lett. 2019, 19, 7866–7876.
- 52W. Wang, P. Wang, F. Shen, C. Gao, J. Yang, ACS Nano 2024. 18, 5656–5671.
