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

作　　者：Ping Sun Zimu Li Dan Zhang Wenfeng Zeng Yi Zheng Lin Mei Hongzhong Chen Nansha Gao Xiaowei Zeng 

机构地区：[1]School of Pharmaceutical Sciences(Shenzhen),Sun Yat-sen University,Shenzhen 518107,China [2]Central Laboratory,University of Chinese Academy of Sciences-Shenzhen Hospital,Shenzhen 518106,China [3]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

出　　处：《Chinese Chemical Letters》2024年第1期379-384,共6页中国化学快报（英文版）

基　　金：the National Natural Science Foundation of China(Nos.32071342 and 32101065);the Natural Science Foundation of Guangdong Province(Nos.2023A1515012015,2022A1515110271 and 2020A1515011353).

摘　　要：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.

关 键 词：Oxaliplatin prodrug Mesoporous polydopamine Charge reversal Synergetic therapy Cancer nanotechnology 

分 类 号：R730.5[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]