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Cellular uptake and intracellular trafficking of PEG-b-PLA polymeric micelles.

Abstract：

:Besides as an inert carrier for hydrophobic anticancer agents, polymeric micelles composed of di-block copolymer poly(ethylene glycol)-poly(lactic acid) (PEG-b-PLA) function as biological response modifiers including reversal of multidrug resistance in cancer. However, the uptake mechanisms and the subsequent intracellular trafficking remain to be elucidated. In this paper, we found that the uptake of PEG-b-PLA polymeric micelles incorporating nile red (M-NR) was significantly inhibited by both dynamin inhibitor dynasore and dynamin-2 dominant negative mutant (dynamin-2 K44A). Exogenously expressed caveolin-1 colocalized with M-NR and upregulated M-NR internalization in HepG2 cells expressing low level of endogenous caveolin-1, while caveolin-1 dominant negative mutant (caveolin-1 Y14F) significantly downregulated M-NR internalization in C6 cells expressing high level of endogenous caveolin-1. Exogenously expressed clathrin light chain A (clathrin LCa) did not mainly colocalize with the internalized M-NR and had no effect on M-NR uptake. These results suggested that dynamin- and caveolin-dependent but clathrin-independent endocytosis was involved in M-NR cellular uptake. We further found that M-NR colocalized with lysosome and microtubulin after internalization.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Zhang Z,Xiong X,Wan J,Xiao L,Gan L,Feng Y,Xu H,Yang X

doi

10.1016/j.biomaterials.2012.06.045

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

7233-40

issue

29

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(12)00695-3

journal_volume

33

pub_type

杂志文章

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