Construction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on T cell regulation
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nstruction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on T cell regulation 1,2†
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Yun Zhang , Yanfang Yang , Jun Ye , Yue Gao , Hengfeng Liao , Junzhuo Zhou , 1,2 1,2 1,2 1 1,2 1,2* Yu Feng , Dongdong Liu , Yingying Meng , Xiaoguang Chen , Lili Gao & Yuling Liu 1
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical 2
Sciences & Peking Union Medical College, Beijing 100050, China; 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 Received April 28, 2020; accepted July 10, 2020; published online September 29, 2020
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. chlorogenic acid, PEGylated liposomes, T cell regulation, immunotherapy Citation:
Zhang, Y., Yang, Y., Ye, J., Gao, Y., Liao, H., Zhou, J., Feng, Y., Liu, D., Meng, Y., Chen, X., et al. (2020). Construction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on T cell regulation. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1739-6
INTRODUCTION Currently, cancer is one of the major diseases responsible for worldwide mortalities. Although cytotoxic chemotherapy is a hallmark of cancer treatment, its limited therapeutic advantage, as well as significant adverse effects, hinder further development. Furthermore, the complex tumor microenvironment (TME) often renders chemotherapy ineffective †Contributed equally to this work *Corresponding author (email:
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