Activatable NIR‐II Photothermal Lipid Nanoparticles for Improved Messenger RNA Delivery

Author:

Li Benhao12,Zhao Mengyao12,Lai Weiping3,Zhang Xuanbo1,Yang Bowei1,Chen Xiaoyuan1245ORCID,Ni Qianqian124

Affiliation:

1. Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering Yong Loo Lin School of Medicine and Faculty of Engineering National University of Singapore Singapore 119074 Singapore

2. Nanomedicine Translational Research Program NUS Centre for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore

3. Department of Chemistry State Key Laboratory of Molecular Engineering of Polymers and iChem Shanghai Key Laboratory of Molecular Catalysis and Innovative Material Fudan University Shanghai 200433 China

4. Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore

5. Institute of Molecular and Cell Biology Agency for Science, Technology, and Research (A*STAR) Singapore 138673 Singapore

Abstract

AbstractEndosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near‐infrared (NIR‐II) lipid nanoparticles (LNPs) containing pH activatable NIR‐II dye conjugated lipid (Cy‐lipid) for potentiating mRNA delivery efficiency via a stimulus‐responsive photothermal‐promoted endosomal escape delivery (SPEED) strategy. In acidic endosomal microenvironment, Cy‐lipid is protonated and turns on NIR‐II absorption for light‐to‐heat transduction mediated by 1064 nm laser irradiation. Then, the heat‐promoted LNPs morphology change triggers rapid escape of NIR‐II LNPs from the endosome, allowing about 3‐fold enhancement of enhanced green fluorescent protein (eGFP) encoding mRNA translation capacity compared to the NIR‐II light free group. In addition, the bioluminescence intensity induced by delivered luciferase encoding mRNA in the mouse liver region shows positive correlation with incremental radiation dose, indicating the validity of the SPEED strategy.

Funder

National University of Singapore

Publisher

Wiley

Subject

General Chemistry,Catalysis

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