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

作者机构：School of Pharmaceutical Sciences(Shenzhen)Sun Yat-sen UniversityShenzhen 518107China Central LaboratoryUniversity of Chinese Academy of Sciences-Shenzhen HospitalShenzhen 518106China Tianjin Key Laboratory of Biomedical MaterialsKey Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2024年第35卷第1期

页      面：379-384页

核心收录：

学科分类：1002[医学-临床医学] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 0702[理学-物理学] 

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) 

主　　题：Oxaliplatin prodrug Mesoporous polydopamine Charge reversal Synergetic therapy Cancer nanotechnology 

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 ***-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 *** 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 *** 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 *** conclusion,the novel nanoplatform-mediated chemo/photothermal/immunotherapy has promising clinical applications in the treatment of malignant tumors.