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Exploiting lipid raft transport with membrane targeted nanoparticles: A strategy for cytosolic drug delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
11045 714 2008 9 PDF Available
Title
Exploiting lipid raft transport with membrane targeted nanoparticles: A strategy for cytosolic drug delivery
Abstract

The ability to specifically deliver therapeutic agents to selected cell types while minimizing systemic toxicity is a principal goal of nanoparticle-based drug delivery approaches. Numerous cellular portals exist for cargo uptake and transport, but after targeting, intact nanoparticles typically are internalized via endocytosis prior to drug release. However, in this work, we show that certain classes of nanoparticles, namely lipid-coated liquid perfluorocarbon emulsions, undergo unique interactions with cells to deliver lipophilic substances to target cells without the need for entire nanoparticle internalization. To define the delivery mechanisms, fluorescently-labeled nanoparticles complexed with αvβ3-integrin targeting ligands were incubated with αvβ3-integrin expressing cells (C32 melanoma) under selected inhibitory conditions that revealed specific nanoparticle-to-cell interactions. We observed that the predominant mechanism of lipophilic delivery entailed direct delivery of lipophilic substances to the target cell plasma membrane via lipid mixing and subsequent intracellular trafficking through lipid raft-dependent processes. We suggest that local drug delivery to selected cell types could be facilitated by employing targeted nanoparticles designed specifically to utilize alternative membrane transport mechanisms.

Keywords
Drug delivery; Nanoparticle; Confocal microscopy; Molecular imaging; Membrane fusion; Lipid exchange
First Page Preview
Exploiting lipid raft transport with membrane targeted nanoparticles: A strategy for cytosolic drug delivery
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 23, August 2008, Pages 3367–3375
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering