Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy  

作　　者：An Lu Yuhao Guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu Huining He Zhiyu Wang Jian-Cheng Wang 

机构地区：[1]Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems,State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China [2]Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics,School of Pharmacy,Tianjin Medical University,Tianjin 300070,China [3]Department of Immuno-oncology,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China [4]Department of Pharmacy,Clinical Trial Research Center,China-Japan Friendship Hospital,Beijing 100029,China [5]Laboratory of innovative formulations and pharmaceutical excipients,Ningbo Institute of Marine Medicine,Peking University,Ningbo 315832,China

出　　处：《Chinese Chemical Letters》2024年第6期385-391,共7页中国化学快报（英文版）

基　　金：financial support from the Basic Research Cooperation Project of Beijing,Tianjin,Hebei from the Natural Science Foundation of Beijing(No.J200018),Tianjin(No.20JCZXJC00070),and Hebei(No.H2020206649);Beijing Natural Science Foundation(No.7214281);the projects of National Natural Science Foundation of China(No.81973259)。

摘　　要：Immunosuppressive microenvironments present critical problems in clinical chemotherapy.To regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied clinically.In this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for chemo-immunotherapy.In vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by macrophages.Furthermore,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint inhibition.The Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关 键 词：CHEMO-IMMUNOTHERAPY Immune checkpoint inhibition Gene silencing MIRIPLATIN Macrophage phagocytosis Nanotechnology 

分 类 号：TQ460.1[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程] R730.51[医药卫生—肿瘤]