期刊
BIOMATERIALS
卷 29, 期 23, 页码 3367-3375出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.04.030
关键词
drug delivery; nanoparticle; confocal microscopy; molecular imaging; membrane fusion; lipid exchange
资金
- NCI NIH HHS [U54 CA136398-010003, U54 CA119342-04, U54 CA119342-01, U54 CA119342-02, U54 CA119342-040001, U54 CA119342-03, U54 CA119342, CO-37007, U54 CA136398, U54-CA-119342] Funding Source: Medline
- NHLBI NIH HHS [HL-073646, R01 HL078631-04, R01 HL073646-04, R01 HL078631-03, R01 HL073646-01A1, R01 HL078631-01, R01 HL073646-03, R01 HL073646-05, R01 HL073646-02, HL-078631, R01 HL078631, R01 HL078631-02, R01 HL073646] Funding Source: Medline
- NIAID NIH HHS [N01CO37007] Funding Source: Medline
- NINDS NIH HHS [R01 NS059302-01, R01 NS059302-02, R01 NS059302] Funding Source: Medline
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 enclocytosis 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 alpha(v)beta(3)-integrin targeting ligands were incubated with alpha(v)beta(3)-integrin expressing cells (O-2 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. (c) 2008 Elsevier Ltd. All rights reserved.
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