Surface Characteristics of Nanoparticles Determine Their Intracellular Fate in and Processing by Human Blood–Brain Barrier Endothelial Cells In Vitro

Abstract

A polarized layer of endothelial cells that comprises the blood-brain barrier (BBB) precludes access of systemically administered medicines to brain tissue. Consequently, there is a need for drug delivery vehicles that mediate transendothelial transport of such medicines. Endothelial cells use a variety of endocytotic pathways for the internalization of exogenous materials, including clathrin-mediated endocytosis, caveolar endocytosis, and macropinocytosis. The different modes of endocytosis result in the delivery of endocytosed material to distinctive intracellular compartments and therewith correlated differential processing. To obtain insight into the properties of drug delivery vehicles that direct their intracellular processing in brain endothelial cells, we investigated the intracellular processing of fixed-size nanoparticles in an in vitro BBB model as a function of distinct nanoparticle surface modifications. Caveolar endocytosis, adsorptive-mediated endocytosis, and receptor-mediated endocytosis were promoted by the use of uncoated 500-nm particles, attachment of the cationic polymer polyethyleneimine (PEI), and attachment of prion proteins, respectively. We demonstrate that surface modifications of nanoparticles, including charge and protein ligands, affect their mode of internalization by brain endothelial cells and thereby their subcellular fate and transcytotic potential.

Magnetic field enhanced convective diffusion of iron oxide nanoparticles in an osmotically disrupted cell culture model of the blood–brain barrier

“…52,53 Examination of transcytosis in cell culture models of the BBB show relatively low permeability with prion-labeled NPs (ie, 6% flux) and cationic polyethylenimine-coated NPs (ie, 3.4% flux) after 18-hour permeability studies. 54 These permeability rates are consistent with the low permeability observed for the positively charged AmS-IONPs in the present study.…”

Biomolecular coronas provide the biological identity of nanosized materials

“…There have also been suggestions that surface biomolecules (including adsorbed endogenous proteins) could influence the crossing of biological barriers, such as the blood-brain barrier 35,58,59 . Mastering these phenomena will have deep implications for both nanosafety and nanotherapeutics 4 .…”

Blood-Brain Barrier and Effectiveness of Therapy Against Brain Tumors

“…It is deemed that the properties of drug delivery vehicles can direct the intracellular processing in brain endothelial cells. Using fixed-size NPs, it has been shown that surface modifications of nanoparticles (e.g., charge and protein ligands) can affect their mode of internalization by BCECs and thereby the subcellular fate (Georgieva et al, 2011).…”