The encapsulation of therapeutic proteins into nanoparticles has been extensively studied for stabilization, sustained release, and targeted <i>in vivo</i> delivery. However, its practical application has been limited by the low encapsulation efficiency and inactivation of proteins in harsh encapsulation processes with free radicals, organic solvents, high temperature, pressure, and shear forces. Here we introduce novel multilamellar protein-lipid hybrid nanovesicles (MPLVs) prepared by the protein-induced metamorphosis of large unilamellar vesicles (LUVs). The MPLVs have a mean diameter of 150-200 nm with a very high loading efficiency of proteins up to 99 % under ambient conditions. The proteins in MPLVs exhibit long-term structural, chemical, and biological stability compared to free proteins. Morphological changes of lipid nanovesicles are investigated with small-angle X-ray scattering, cryogenic transmission electron microscopy, and Förster resonance energy transfer. Surface pressure isotherm and molecular dynamics simulation are performed to suggest the self-assembly mechanism of proteins with LUVs. This study suggests a promising highly effective therapeutic protein delivery platform with long-term stabilization of proteins in mild conditions.

Multilamellar hybrid nanovesicles <i>via</i> protein-induced self-assembly of unilamellar lipid vesicles

ACS Spring Meeting 2021

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Multilamellar hybrid nanovesicles via protein-induced self-assembly of unilamellar lipid vesicles