中国化学快报(英文版)2024，Vol.35Issue(6) ：385-391.DOI:10.1016/j.cclet.2023.108928

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

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
中国化学快报(英文版)2024，Vol.35Issue(6) ：385-391.DOI:10.1016/j.cclet.2023.108928
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Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 siRNA for enhancing tumor therapy

An Lu 1Yuhao Guo 1Yi Yan 1Lin Zhai 1Xiangyu Wang 1Weiran Cao 2Zijie Li 3Zhixia Zhao 4Yujie Shi 1Yuanjun Zhu 1Xiaoyan Liu 1Huining He 2Zhiyu Wang 3Jian-Cheng Wang5
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作者信息

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

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.

Key words

Chemo-immunotherapy/Immune checkpoint inhibition/Gene silencing/Miriplatin/Macrophage phagocytosis/Nanotechnology

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基金项目

Basic Research Cooperation Project of Beijing,Tianjin,Hebei from the Natural Science Foundation of Beijing(J200018)

Tianjin(20JCZXJC00070)

Hebei(H2020206649)

Beijing Natural Science Foundation(7214281)

projects of National Natural Science Foundation of China(81973259)

出版年

2024
中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCDCSCD
影响因子：0.771
ISSN：1001-8417
参考文献量27
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