Issue 44, 2017

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles

Abstract

Following exposure to biological milieus (e.g. after systemic administration), nanoparticles (NPs) get covered by an outer biomolecular corona (BC) that defines many of their biological outcomes, such as the elicited immune response, biodistribution, and targeting abilities. In spite of this, the role of BC in regulating the cellular uptake and the subcellular trafficking properties of NPs has remained elusive. Here, we tackle this issue by employing multicomponent (MC) lipid NPs, human plasma (HP) and HeLa cells as models for nanoformulations, biological fluids, and target cells, respectively. By conducting confocal fluorescence microscopy experiments and image correlation analyses, we quantitatively demonstrate that the BC promotes a neat switch of the cell entry mechanism and subsequent intracellular trafficking, from macropinocytosis to clathrin-dependent endocytosis. Nano-liquid chromatography tandem mass spectrometry identifies apolipoproteins as the most abundant components of the BC tested here. Interestingly, this class of proteins target the LDL receptors, which are overexpressed in clathrin-enriched membrane domains. Our results highlight the crucial role of BC as an intrinsic trigger of specific NP–cell interactions and biological responses and set the basis for a rational exploitation of the BC for targeted delivery.

Graphical abstract: An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles

Supplementary files

Article information

Article type
Paper
Submitted
29 aug 2017
Accepted
28 sep 2017
First published
18 okt 2017

Nanoscale, 2017,9, 17254-17262

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles

L. Digiacomo, F. Cardarelli, D. Pozzi, S. Palchetti, M. A. Digman, E. Gratton, A. L. Capriotti, M. Mahmoudi and G. Caracciolo, Nanoscale, 2017, 9, 17254 DOI: 10.1039/C7NR06437C

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