Construction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on T cell regulation

查看全文 作　　者：Yun [1,2]Zhang;Yanfang [1,2]Yang;Jun [1,2]Ye;Yue [1,2]Gao;Hengfeng [1,2]Liao;Junzhuo [1,2]Zhou;Yu [1,2]Feng;Dongdong [1,2]Liu;Yingying [1,2]Meng;Xiaoguang [1]Chen;Lili [1,2]Gao;Yuling [1,2]Liu

机构地区：[1]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China;[2]Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China

出　　处：《Science China(Life Sciences)》索引2021年第64卷第7期,共19页

基　　金：financial support from the National Megaproject for Innovative Drugs(2018ZX09711001 and 2018ZX09721003)of the Chinese government;Graduate Student Innovation Fund of PUMC(2018-1007-01);CAMS Innovation Fund for Medical Sciences(CIFMS-2019-I2M-1-005)。 摘　　要：As a potential cancer immunotherapeutic agent,chlorogenic acid(CHA)has entered phase II clinical trials in China as a lyophilized powder formulation for treating glioma.However,the in vivo instability of CHA necessitates daily intramuscular injections,resulting in patient noncompliance.In this study,CHA-phospholipid complex(PC)-containing PEGylated liposomes(CHA-PC PEG-Lipo,named as CPPL),with CHA-PC as the drug intermediate,were prepared to lower the administration frequency.CPPL demonstrated excellent physicochemical properties,enhanced tumor accumulation,and inhibited tumor growth even when the administration interval was prolonged to 4 days when compared to a CHA solution and CHA-PC loaded liposomes(CHA-PC Lipo,labeled as CPL),both of which only demonstrated antitumor efficacy with once-daily administration.Further evaluation of the in vivo antitumor immune mechanism suggested that the extended antitumor immune efficacy of CPPL could be attributed to its distinct immune-stimulating mechanism when compared with CHA solution and CPL,such as stimulating both CD4+and CD8+T cell infiltration,inhibiting myeloid-derived suppressor cell expression,reducing the expression of Th2 related factors,and notably,increasing the memory T cells in tumor tissues.This CHA-containing formulation could reduce the frequency of in vivo CHA administration during cancer treatment via T cells,especially memory T cell regulation. 关键词：chlorogenic acid PEGylated liposomes T cell regulation IMMUNOTHERAPY

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Construction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on T cell regulation

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