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Activatable NIR-II Photothermal Lipid Nanoparticles for Improved Messenger RNA Delivery |
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| Authors: | Dr. Benhao Li Dr. Mengyao Zhao Weiping Lai Dr. Xuanbo Zhang Bowei Yang Prof. Xiaoyuan Chen Prof. Qianqian Ni |
| 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 Nanomedicine Translational Research Program, NUS Centre for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597 Singapore These authors contributed equally to this work. Contribution: Investigation (lead), Writing - original draft (lead);2. 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 Nanomedicine Translational Research Program, NUS Centre for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597 Singapore These authors contributed equally to this work. Contribution: Investigation (supporting);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 Contribution: Investigation (supporting);4. 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 Contribution: Investigation (supporting);5. 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 |
| Abstract: | Endosomal 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 s timulus-responsive p hotothermal-promoted e ndosomal e scape d elivery (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. |
| Keywords: | Endosomal Escape Lipid Nanoparticle Photothermal Effect Second Near-Infrared Window |