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Targeted delivery of chlorogenic acid by mannosylated liposomes to effectively promote the polarization of TAMs for the treatment of glioblastoma

查看全文 作　　者：Jun [1,2]Ye;Yanfang [1,2]Yang;Jing [1]Jin;Ming [1]Ji;Yue [1,2]Gao;Yu [1,2]Feng;Hongliang [1,2]Wang;Xiaoguang [1]Chen;Yuling [1,2]Liu 高影响力作者 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,PR 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,PR China高影响力机构 出　　处：《Bioactive Materials》索引2020年第5卷第3期,共15页高影响力期刊 基　　金：financially supported by the National Science and Technology Major Project of China(Grant No.2018ZX09721003 , 2018ZX09711001);the Fundamental Research Funds for the Central Universities(Grant No.3332019069);the Young Scientists Fund of the National Natural Science Foundation of China(Grant No.81703566). 摘　　要：Tumor-associated macrophages(TAMs)generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis,suggesting their potential value as a target in cancer immunotherapy.Chlorogenic acid(CHA)has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype.However,rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials.In this study,mannosylated liposomes are developed for targeted delivery of CHA to TAMs.The immunoregulatory effects of CHA,along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes,are investigated through in vitro and in vivo experiments.The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size,favorable stability,and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects.Further,CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype.Overall,these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype. 关 键 词：Chlorogenic acid Mannosylated liposome Tumor-associated macrophage Cancer immunotherapy Drug delivery
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