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

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外文摘要：Immunosuppressive microenvironments present critical problems in clinical chemotherapy.To regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune check-point 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 siRNA(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 pro-mote the phagocytosis of tumor cells by macrophages.Furthermore,in vivo results revealed that Lip-Pt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of MiPt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor effi-ciency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of MiPt 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 phagocyto-sis and immune checkpoint inhibition.The Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

外文关键词：

Chemo-immunotherapyImmune checkpoint inhibitionGene silencingMiriplatinMacrophage phagocytosisNanotechnology

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

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作者单位：

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

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics,School of Pharmacy,Tianjin Medical University,Tianjin 300070,China

Department of Immuno-oncology,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China

Department of Pharmacy,Clinical Trial Research Center,China-Japan Friendship Hospital,Beijing 100029,China

Laboratory of innovative formulations and pharmaceutical excipients,Ningbo Institute of Marine Medicine,Peking University,Ningbo 315832,China

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基金：

Basic Research Cooperation Project of Beijing,Tianjin,Hebei from the Natural Science Foundation of BeijingTianjinHebeiBeijing Natural Science Foundationprojects of National Natural Science Foundation of China

项目编号：

J20001820JCZXJC00070H2020206649721428181973259

出版年：

2024

DOI：

10.1016/j.cclet.2023.108928

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCD

影响因子：0.771

ISSN：1001-8417

年,卷(期)：2024.35(6)