Citation: Ping Sun, Zimu Li, Dan Zhang, Wenfeng Zeng, Yi Zheng, Lin Mei, Hongzhong Chen, Nansha Gao, Xiaowei Zeng. Multifunctional biodegradable nanoplatform based on oxaliplatin prodrug cross-linked mesoporous polydopamine for enhancing cancer synergetic therapy[J]. Chinese Chemical Letters, ;2024, 35(1): 108346. doi: 10.1016/j.cclet.2023.108346 shu

Multifunctional biodegradable nanoplatform based on oxaliplatin prodrug cross-linked mesoporous polydopamine for enhancing cancer synergetic therapy

Ping Sun ^{a, 1} ,
Zimu Li ^{a, 1} ,
Dan Zhang ^{a, 1} ,
Wenfeng Zeng ^a ,
Yi Zheng ^b ,
Lin Mei ^{a, c} ,
Hongzhong Chen ^{a, *,} ,
Nansha Gao ^{a, *,} ,
Xiaowei Zeng ^{a, *,}

a.
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China
b.
Central Laboratory, University of Chinese Academy of Sciences-Shenzhen Hospital, Shenzhen 518106, China
c.
Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China

chenhzh58@mail.sysu.edu.cn

gaonsh@mail.sysu.edu.cn

zengxw23@mail.sysu.edu.cn

Received Date: 14 January 2023
Revised Date: 13 March 2023
Accepted Date: 16 March 2023
Available Online: 24 March 2023

Figures(4)

Due to the limitations of conventional chemotherapy including side effects, poor prognosis, and drug resistance, there is an urgent need for the development of a novel multi-functional combined therapy strategy. Dopamine-modified oxaliplatin prodrug (OXA-DA) was successfully synthesized in this study to ameliorate the organ distribution of oxaliplatin for improving the drug efficacy and reducing toxic side effects, and OXA-DA was applied to develop a porous oxaliplatin cross-linked polydopamine nanoparticle for loading siPD-L1 to construct multifunctional nanoplatform. The multifunctional nanoplatform was modified with poly(2-ethyl-2-oxazoline) (PEOz), which occurred charge reversal in the tumor microenvironment, and exerted the lysosomal escape effect in tumor cells to improve the bioavailability of small interfering RNA targeting programmed cell death-ligand 1 (siPD-L1). The pH-responsive charge reversal, photothermal, biodegradation, lysosomal escape ability, PD-L1 protein degradation, toxicity properties and multiple antitumor effects were comprehensively evaluated in vitro and in vivo experiments. The findings indicated that OXA-DA-siPD-L1@PDA-PEOz excellently induced tumor cell necrosis and apoptosis as a result of the synergistic effect of chemo-photothermal therapy, and upregulated CD8⁺ T cells produced interferon-γ (IFN-γ) to further attack the tumor cells. In conclusion, the novel nanoplatform-mediated chemo/photothermal/immunotherapy has promising clinical applications in the treatment of malignant tumors.
- Oxaliplatin prodrug,
- Mesoporous polydopamine,
- Charge reversal,
- Synergetic therapy,
- Cancer nanotechnology
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