Lipid-mRNA Nanoparticle Designed to Enhance Intracellular Delivery Mediated by Shock Waves.

ACS Applied Materials & Interfaces
Jing ZhangTerence H Rabbitts

Abstract

Cellular membranes are, in general, impermeable to macromolecules (herein referred to as macrodrugs, e.g., recombinant protein, expression plasmids, or mRNA), which is a major barrier for clinical translation of macrodrug-based therapies. Encapsulation of macromolecules in lipid nanoparticles (LNPs) can protect the therapeutic agent during transport through the body and facilitate the intracellular delivery via a fusion-based pathway. Furthermore, designing LNPs responsive to stimuli can make their delivery more localized, thus limiting the side effects. However, the principles and criteria for designing such nanoparticles remain unclear. We show that the thermodynamic state of the lipid membrane of the nanoparticle is a key design principle for acoustically responsive fusogenic nanoparticles. We have optimized a cationic LNP (designated LNPLH) with two different phase transitions near physiological conditions for delivering mRNA. A bicistronic mRNA encoding a single domain intracellular antibody fragment and green fluorescent protein (GFP) was introduced into a range of human cancer cell types using LNPLH, and the protein expression was measured via fluorescence corresponding to the GFP expression. The LNPLH/mRNA complex demon...Continue Reading

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Citations

Jun 26, 2020·Frontiers in Bioengineering and Biotechnology·Luisa RaccaValentina Cauda
Jun 28, 2020·Nature Communications·Nicolas BeryTerry Rabbitts
Oct 19, 2020·Journal of Nanobiotechnology·Yinan ZhaoShubiao Zhang
May 1, 2021·Life·Jayan D M Senevirathna, Shuichi Asakawa
Jun 18, 2021·Nano-micro Letters·Luisa Racca, Valentina Cauda
Jun 8, 2021·Current Opinion in Colloid & Interface Science·Jessica HuangAngus P R Johnston
Jul 20, 2021·Chemical Reviews·Yuebao ZhangYizhou Dong
Aug 17, 2021·Nature Reviews. Materials·Xucheng HouYizhou Dong

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Methods Mentioned

BETA
transfection
infrared spectroscopy
RNA assay
fluorescence
flow cytometry
in vitro transcription
flow
confocal
Assay
differential light scattering

Software Mentioned

FlwoJo

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