Dynamics of receptor-mediated nanoparticle internalization into endothelial cells

Nanoparticles offer a promising medical tool for targeted drug delivery, for example to treat inflamed endothelial cells during the development of atherosclerosis. To inform the design of such therapeutic strategies, we develop a computational model of nanoparticle internalization into endothelial c...

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Bibliographic Details
Published in:PloS one 2015-04, Vol.10 (4), p.e0122097-e0122097
Main Authors: Gonzalez-Rodriguez, David, Barakat, Abdul I
Format: Article
Language:English
Subjects:
Analysis
Arteriosclerosis
Atherosclerosis
Atherosclerosis - drug therapy
Atherosclerosis - metabolism
Binding
Cell Membrane - metabolism
Computer applications
Cytoplasm
Drug delivery
Drug delivery systems
Endocytosis
Endothelial cells
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Endothelium
Fluid mechanics
Health aspects
Humans
Inflammation
Intercellular adhesion molecule 1
Intercellular Adhesion Molecule-1 - metabolism
Internalization
Kinetics
Mechanical properties
Mechanics
Models, Biological
Nanoparticles
Nanoparticles - metabolism
Physics
Receptors
Receptors, Cell Surface - antagonists & inhibitors
Receptors, Cell Surface - metabolism
Stress concentration
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Summary:Nanoparticles offer a promising medical tool for targeted drug delivery, for example to treat inflamed endothelial cells during the development of atherosclerosis. To inform the design of such therapeutic strategies, we develop a computational model of nanoparticle internalization into endothelial cells, where internalization is driven by receptor-ligand binding and limited by the deformation of the cell membrane and cytoplasm. We specifically consider the case of nanoparticles targeted against ICAM-1 receptors, of relevance for treating atherosclerosis. The model computes the kinetics of the internalization process, the dynamics of binding, and the distribution of stresses exerted between the nanoparticle and the cell membrane. The model predicts the existence of an optimal nanoparticle size for fastest internalization, consistent with experimental observations, as well as the role of bond characteristics, local cell mechanical properties, and external forces in the nanoparticle internalization process.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0122097