DataVXAdvanced MaterialsPaper
journal article·2023-11Open access

Esterase‐Labile Quaternium Lipidoid Enabling Improved mRNA‐LNP Stability and Spleen‐Selective mRNA Transfection

Runnan Zhang, Shiqun Shao, Ying Piao, Jiajia Xiang, Xuyong Wei, Zhen Zhang, Zhuxian Zhou, Jianbin Tang, Nasha Qiu, Xiao Xu, Yanpeng Liu, Youqing Shen

Advanced Materials· Volume 35· Issue 46
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Source abstract

Abstract

Abstract 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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Research context

Nanomaterials

OpenAlex topics: RNA Interference and Gene Delivery · Advanced biosensing and bioanalysis techniques · Nanoparticle-Based Drug Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering College of Chemical and Biological Engineering Zhejiang University Hangzhou 310058 China

Key Laboratory of Biomass Chemical Engineering of the Ministry of Education College of Chemical and Biological Engineering Zhejiang University Hangzhou 310058 China

ZJU‐Hangzhou Global Scientific and Technological Innovation Center 311215 Hangzhou China

The Center for Integrated Oncology and Precision Medicine of Zhejiang Province Affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine Hangzhou 310006 China

Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Hangzhou 310006 China

Zhejiang Longcharm Bio‐tech Pharma Co., Ltd. Hangzhou 310018 China

Zhejiang University School of Medicine Hangzhou 310058 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Key Research and Development Program of Zhejiang Province · Fundamental Research Funds for the Central Universities

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