In situ oxidative polymerization of platinum(IV) prodrugs in pore-confined spaces of CaCO3 nanoparticles for cancer chemoimmunotherapy

Fangmian Wei; Libing Ke; Siyuan Gao; Johannes Karges; Jinquan Wang; Yu Chen; Liangnian Ji; Hui Chao

doi:10.1039/D3SC02264A

In situ oxidative polymerization of platinum(iv) prodrugs in pore-confined spaces of CaCO₃ nanoparticles for cancer chemoimmunotherapy†

Fangmian Wei,^a Libing Ke,^a Siyuan Gao,^a Johannes Karges,

^b Jinquan Wang,^c Yu Chen,

^a Liangnian Ji^a and Hui Chao

*^ad

Author affiliations

* Corresponding authors

^a MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P. R. China
E-mail: ceschh@mail.sysu.edu.cn

^b Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany

^c Guangdong Provincial Key Laboratory of Biotechnology Drug Candidate, Guangdong Pharmaceutical University, Guangzhou, China

^d MOE Key Laboratory of Theoretical Organic Chemistry and Functional Molecule, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, P. R. China

Abstract

Drug resistance and metastases are the leading causes of death in clinics. To overcome this limitation, there is an urgent need for new therapeutic agents and drug formulations that are able to therapeutically intervene by non-traditional mechanisms. Herein, the physical adsorption and oxidative polymerization of Pt(IV) prodrugs in pore-confined spaces of CaCO₃ nanoparticles is presented, and the nanomaterial surface was coated with DSPE-PEG₂₀₀₀-Biotin to improve aqueous solubility and tumor targeting. While the nanoparticle scaffold remained stable in an aqueous solution, it quickly degraded into Ca²⁺ in the presence of acid and into cisplatin in the presence of GSH. The nanoparticles were found to interact in cisplatin-resistant non-small lung cancer cells by a multimodal mechanism of action involving mitochondrial Ca²⁺ overload, dual depletion of GSH, nuclear DNA platination, and amplification of ROS and lipid peroxide generation, resulting in triggering cell death by a combination of apoptosis, ferroptosis and immunogenic cell death in vitro and in vivo. This study could present a novel strategy for the treatment of drug-resistant and metastatic tumors and therefore overcome the limitations of currently used therapeutic agents in the clinics.

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Article information

DOI: https://doi.org/10.1039/D3SC02264A
Article type: Edge Article
Submitted: 03 May 2023
Accepted: 01 Jun 2023
First published: 02 Jun 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry

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Chem. Sci., 2023,14, 7005-7015

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In situ oxidative polymerization of platinum(IV) prodrugs in pore-confined spaces of CaCO₃ nanoparticles for cancer chemoimmunotherapy

F. Wei, L. Ke, S. Gao, J. Karges, J. Wang, Y. Chen, L. Ji and H. Chao, Chem. Sci., 2023, 14, 7005 DOI: 10.1039/D3SC02264A

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