Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy  

作　　者：Jianjun Cheng Haitian Zhao Bin Li Hua Zhang Qianyu Zhao Shiyao Fu Ying Han Weihong Lu Jiahua Shi Xin Yang 

机构地区：[1]School of Medicine and Health,Harbin Institute of Technology,Harbin 150001,China [2]Academician Workstation,Jiangxi University of Chinese Medicine,Nanchang 330004,China [3]School of Chemistry and Chemical Engineering,Harbin Institute of Technology,Harbin 150001,China [4]Chongqing Research Institute,Harbin Institute of Technology,Chongqing 401135,China [5]National and Local Joint Engineering Laboratory for Synthesis,Transformation and Separation of Extreme Environmental Nutrients,Harbin 150001,China [6]Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province,Henan University,Kaifeng 475004,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第2期879-896,共18页药学学报（英文版）

基　　金：the financial support from the National Natural Science Foundation of China(No.31972040,81760708);Jiangxi Provincial Natural Science Foundation Key Project(No.20192ACBL20028,China)。

摘　　要：Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment.However,developing multifunctional biodegradable,biocompatible,low-toxic but highly efficient,and clinically available transformed nano-immunostimulants remains a challenge and is in great demand.Herein,we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid(BA),a water-soluble chitosan oligosaccharide(COS),and a low toxic photosensitizer chlorin e6(Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy.We show that the designed nanodrugs harbored a smart and distinctive“dormancy”characteristic in chemotherapeutic effect with desired lower cytotoxicity,and multiple favorable therapeutic features including improved^(1)O_(2)generation induced by the reduced energy gap of Ce6,pH-responsiveness,good biodegradability,and biocompatibility,ensuring a highly efficient,synergistic photochemotherapy.Moreover,when combined with anti-PD-L1 therapy,both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy(PDT)could effectively activate antitumor immunity when treating primary or distant tumors,opening up potentially attractive possibilities for clinical immunotherapy.

关 键 词：Cancer immunotherapy Nano-immunostimulants Chemotherapeutic dormancy PRO-DRUG Self-assembly Natural small molecule Betulinic acid Photodynamic therapy 

分 类 号：R730.51[医药卫生—肿瘤]