PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines

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外文摘要：Dendritic cell(DC)-targeted delivery of mRNA is a prominent method to boost the efficacy of mRNA tu-mor vaccines.The targeting ligands are often modified on nanocarriers by polyethylene glycol(PEG)linker in mRNA delivery systems.Whether the PEG linker length influences the targeting delivery efficiency of mRNA nanocarrier in vivo remains unclear.Here,we designed and constructed DC-targeted mRNA deliv-ery systems modified by mannose via different PEG linker lengths(100/400/1000/2000)(MPn-LPX).The top candidate MP400-LPX(the linker was PEG400)showed the optimal mRNA expression and antigen presentation owing to the highly efficient uptake by DCs.Furthermore,MP400-LPX could better inhib-ited tumor growth and extended survival in the E.G7-OVA lymphoma and TC-1 cervical tumor mouse model.Collectively,these results demonstrated that PEG400 was the optimal linker for the PEGylated DC-targeted mRNA vaccines.Our findings provided a new platform for the rational design of targeted mRNA nanovaccines with shorter-length PEG.

外文关键词：

Cancer immunotherapymRNA vaccinesDC-targeted deliveryPEGylated liposomesCellular uptake

作者：

Wen Xiao、Fazhan Wang、Yangzhuo Gu、Xi He、Na Fan、Qian Zheng、Shugang Qin、Zhongshan He、Yuquan Wei、Xiangrong Song

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作者单位：

Department of Critical Care Medicine,Frontiers Science Center for Disease-related Molecular Network,State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China

Medical Research Center,The First Affiliated Hospital of Zhengzhou University,Zhengzhou University,Zhengzhou 450000,China

基金：

National Key Science and Technology Special ProjectsHenan Medical Science and Technology Joint Building Program中国博士后科学基金Henan Province Youth Talent Promoting ProjectKey Research and Development Project of Henan ProvinceSichuan Provincial Science and Technology Innovation(Seedling Project)Cultivation Projects

项目编号：

2018ZX09201018-024SBGJ2021021322020TQ02822022HYTP047232102311224MZGC20230034

出版年：

2024

DOI：

10.1016/j.cclet.2023.108755

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(5)

参考文献量42