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

Benhao Li; Mengyao Zhao; Weiping Lai; Xuanbo Zhang; Bowei Yang; Xiaoyuan Chen; Qianqian Ni

doi:10.1002/anie.202302676

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

Angew Chem Int Ed Engl. 2023 Jun 19;62(25):e202302676. doi: 10.1002/anie.202302676. Epub 2023 May 9.

Authors

Benhao Li^{1

2}, Mengyao Zhao^{1

2}, Weiping Lai³, Xuanbo Zhang¹, Bowei Yang¹, Xiaoyuan Chen^{1

2

4

5}, Qianqian Ni^{1

2

4}

Affiliations

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.

PMID: 37074038
DOI: 10.1002/anie.202302676

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 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.

Keywords: Endosomal Escape; Lipid Nanoparticle; Photothermal Effect; Second Near-Infrared Window.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Lipids
Liposomes*
Mice
Nanoparticles*
Phototherapy
RNA, Messenger

Substances

Lipid Nanoparticles
RNA, Messenger
Liposomes
Lipids