PEGylation-Dependent Cell Uptake of Lipid Nanoparticles Revealed by Spatiotemporal Correlation Spectroscopy.

Autor:	Digiacomo L; NanoDelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy., Renzi S; NanoDelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy., Pirrottina A; NanoDelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy., Amenitsch H; Institute of Inorganic Chemistry, Graz University of Technology, 8010 Graz, Austria., De Lorenzi V; Laboratorio NEST, Scuola Normale Superiore, 56127 Pisa, Italy., Pozzi D; NanoDelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy., Cardarelli F; Laboratorio NEST, Scuola Normale Superiore, 56127 Pisa, Italy., Caracciolo G; NanoDelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2024 Sep 05; Vol. 7 (10), pp. 3004-3010. Date of Electronic Publication: 2024 Sep 05 (Print Publication: 2024).
DOI:	10.1021/acsptsci.4c00419
Abstrakt:	Polyethylene glycol (PEG) is a common surface modification for lipid nanoparticles (LNPs) to improve their stability and in vivo circulation time. However, the impact of PEGylation on LNP cellular uptake remains poorly understood. To tackle this issue, we systematically compared plain and PEGylated LNPs by combining dynamic light scattering, electrophoretic light scattering, and synchrotron small-angle X-ray scattering (SAXS) that unveils a striking similarity in size and core structure but a significant reduction in surface charge. Upon administration to human embryonic kidney (HEK 293) cells, plain and PEGylated LNPs were internalized through different endocytic routes, as revealed by spatiotemporal correlation spectroscopy. An imaging-derived mean square displacement (iMSD) analysis shows that PEGylated LNPs exhibit a significantly stronger preference for caveolae-mediated endocytosis (CAV) and clathrin-mediated endocytosis (CME) pathways compared to plain LNPs, with these latter being better tailored to MCR-dependent internalization and trafficking. This suggests that PEG plays a crucial role in directing LNPs toward specific cellular uptake routes. Further studies should explore how PEG-mediated endocytosis impacts intracellular trafficking and ultimately translates to therapeutic efficacy, guiding the design of next-generation LNP delivery systems. Competing Interests: The authors declare no competing financial interest. (© 2024 American Chemical Society.)
Databáze:	MEDLINE
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