Exploiting lipid raft transport with membrane targeted nanoparticles: A strategy for cytosolic drug delivery
Exploiting lipid raft transport with membrane targeted nanoparticles: A strategy for cytosolic drug delivery
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DOI：
10.1016/j.biomaterials.2008.04.030
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发表时间：
2008-08-01
期刊：
影响因子：
14
通讯作者：
Wickline, Samuel A.
中科院分区：
文献类型：
--
作者：
Partlow, Kathryn C.;Lanza, Gregory M.;Wickline, Samuel A.
能够将治疗剂特异性地递送至选定的细胞类型，同时最小化全身毒性是基于纳米颗粒的药物递送方法的主要目标。存在许多用于货物摄取和运输的细胞门户，但在靶向后，完整的纳米颗粒通常在药物释放之前通过胞吞作用内化。然而，在这项工作中，我们表明某些类别的纳米颗粒，即脂质包被的液体全氟化碳乳液，与细胞发生独特的相互作用，将亲脂性物质递送至靶细胞，而不需要整个纳米颗粒内化。为了确定递送机制，将与 α(v)β(3)-整合素靶向配体复合的荧光标记纳米颗粒与 α(v)β(3)-整合素表达细胞（O-2 黑色素瘤）在选定的抑制条件下孵育，揭示了特定的纳米颗粒与细胞的相互作用。我们观察到，亲脂性递送的主要机制需要通过脂质混合将亲脂性物质直接递送至靶细胞质膜，并随后通过脂筏依赖性过程进行细胞内运输。我们建议，通过采用专门设计用于利用替代膜转运机制的靶向纳米颗粒，可以促进局部药物递送至选定的细胞类型。 (c) 2008 Elsevier Ltd. 保留所有权利。
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.