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

Wen Xiao ¹Fazhan Wang ²Yangzhuo Gu ¹Xi He ¹Na Fan ¹Qian Zheng ¹Shugang Qin ¹Zhongshan He ¹Yuquan Wei ¹Xiangrong Song¹

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作者信息

1. 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
2. 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
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Abstract

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.

Key words

Cancer immunotherapy/mRNA vaccines/DC-targeted delivery/PEGylated liposomes/Cellular uptake

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基金项目

National Key Science and Technology Special Projects(2018ZX09201018-024)

Henan Medical Science and Technology Joint Building Program(SBGJ202102132)

中国博士后科学基金(2020TQ0282)

Henan Province Youth Talent Promoting Project(2022HYTP047)

Key Research and Development Project of Henan Province(232102311224)

Sichuan Provincial Science and Technology Innovation(Seedling Project)Cultivation Projects(MZGC20230034)

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42

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