Citation: Wen Xiao, Fazhan Wang, Yangzhuo Gu, Xi He, Na Fan, Qian Zheng, Shugang Qin, Zhongshan He, Yuquan Wei, Xiangrong Song. PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines[J]. Chinese Chemical Letters, ;2024, 35(5): 108755. doi: 10.1016/j.cclet.2023.108755 shu

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

Wen Xiao ^{a, 1} ,
Fazhan Wang ^{a, b, 1} ,
Yangzhuo Gu ^{a, 1} ,
Xi He ^{a, 1} ,
Na Fan ^a ,
Qian Zheng ^a ,
Shugang Qin ^a ,
Zhongshan He ^a ,
Yuquan Wei ^{a, *,} ,
Xiangrong Song ^{a, *,}

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

yqwei@scu.edu.cn

songxr@scu.edu.cn

Received Date: 19 April 2023
Revised Date: 21 June 2023
Accepted Date: 30 June 2023
Available Online: 3 July 2023

Figures(5)

Dendritic cell (DC)-targeted delivery of mRNA is a prominent method to boost the efficacy of mRNA tumor 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 delivery systems modified by mannose via different PEG linker lengths (100/400/1000/2000) (MP_n-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 inhibited 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.
- Cancer immunotherapy,
- mRNA vaccines,
- DC-targeted delivery,
- PEGylated liposomes,
- Cellular uptake
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