Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway

被引:216
作者
Lai, Samuel K.
Hida, Kaoru
Man, Stan T.
Chen, Clive
Machamer, Carolyn
Schroer, Trina A.
Hanes, Justin
机构
[1] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA
[3] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA
[4] Johns Hopkins Univ, Inst NanobioTechnol, Baltimore, MD 21218 USA
[5] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Care Ctr, Dept Oncol, Baltimore, MD 21231 USA
[6] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21231 USA
基金
加拿大自然科学与工程研究理事会;
关键词
intracellular delivery; trafficking; size; gene delivery; non-clathrin; non-caveolae;
D O I
10.1016/j.biomaterials.2007.02.021
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The efficacy of many therapeutic molecules could be greatly enhanced by polymer-based nanoparticle systems capable of delivering them to the direct vicinity of the cell nucleus. However, degradation of the particles and encapsulated drugs within the enzyme-rich and low-pH environments of the endo/lysosomal pathway of cells has dramatically limited the efficacy of such systems. In this paper, we discovered that small polymeric particles (< 25 nm) but not larger particles (> 42 nm) enter live cells via a novel mechanism that leads to trafficking outside the endo/lysosomal pathway. Sub-25 nm particles rapidly transport to the perinuclear region of cells in vesicles that never acidify. The pathway is non-degradative, cholesterol independent, and non-clathrin and non-caveolae mediated. This privileged non-acidic pathway may be general since our results are surprisingly obtained with standard latex polymer beads without addition of ligands and may, therefore, provide a promising route for drug and gene delivery using biomaterial-based nanodevices. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2876 / 2884
页数:9
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