【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,resu
【机 构】
：
State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia M
论文部分内容阅读
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 ex-pression 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.
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