转染
信使核糖核酸
体内
脾脏
癌症免疫疗法
核糖核酸
细胞生物学
生物
免疫系统
免疫疗法
化学
分子生物学
生物化学
免疫学
基因
生物技术
作者
Runnan Zhang,Shiqun Shao,Ying Piao,Jiajia Xiang,Xuyong Wei,Zhen Zhang,Zhuxian Zhou,Jianbin Tang,Nasha Qiu,Xiao Xu,Yanpeng Liu,Youqing Shen
标识
DOI:10.1002/adma.202303614
摘要
Ionizable cationic lipids are recognized as an essential component of lipid nanoparticles (LNPs) for messenger RNA (mRNA) delivery but can be confounded by low lipoplex stability with mRNA during storage and in vivo delivery. Herein, the rational design and combinatorial synthesis of esterase-triggered decationizable quaternium lipid-like molecules (lipidoids) are reported to develop new LNPs with high delivery efficiency and improved storage stability. This top lipidoid carries positive charges at the physiological condition but promptly acquires negative charges in the presence of esterase, thus permitting stable mRNA encapsulation during storage and in vivo delivery while balancing efficient mRNA release in the cytosol. An optimal LNP formulation is then identified through orthogonal optimization, which enables efficacious mRNA transfection selectively in the spleen following intravenous administration. LNP-mediated delivery of ovalbumin (OVA)-encoding mRNA induces efficient antigen expression in antigen-presenting cells and elicits robust antigen-specific immune responses against OVA-transduced tumors. The work demonstrates the potential of decationizable quaternium lipidoids for spleen-selective RNA transfection and cancer immunotherapy.
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