NDLI: Effect of shell-crosslinking of micelles on endocytosis and exocytosis: acceleration of exocytosis by crosslinking

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Biomaterials Science Vol - 1 Issue - 2

Effect of shell-crosslinking of micelles on endocytosis and exocytosis: acceleration of exocytosis by crosslinking

Content Provider	Royal Society of Chemistry (RSC)
Author	Kim, Yoseop Lu, Hongxu Pourgholami, Mohammad H. Morris, David L. Stenzel, Martina H.
Copyright Year	2013
Abstract	Uptake of drug-loaded micelles by tumour cell lines can be the crucial step in the creation of an efficient drug delivery system. Crosslinking of micelles has increasingly been proposed as a pathway to create stable nanoparticles. So far, little is known how crosslinking can affect the interaction of these nanocarriers with cells. The aim of this study is therefore to investigate the effect of crosslinking on exo- and endocytosis. RAFT (reversible addition fragmentation chain transfer) polymerization has been used to synthesize the block copolymer poly(methyl methacrylate)-block-poly(polyethylene glycol methyl ether methacrylate) PMMA-b-P(PEGMEMA), which was subsequently self-assembled into micelles of 20 nm. For comparison, the micelles were shell-crosslinked by incorporating methacrylic acid into the shell, which was used as a reactive group for crosslinking with 1,8-diaminooctane. The hydrodynamic diameter of the shell-crosslinked micelle was with 25 nm similar to that of the non-crosslinked one. Endocytosis of both micelles was significantly reduced by the presence of NaN3 or at 4 °C suggesting an energy dependent process. The internalization pathways of the block copolymer micelles in OVCAR-3 cells were elucidated using endocytosis inhibitors. Both nanoparticles, micelles and shell-crosslinked micelles, were internalized by caveolae mediated endocytosis while clathrin mediated endocytosis did not play a noticeable role. Shell-crosslinking therefore did not have an effect on endocytosis. However, a considerable difference was found in the exocytosis of both particles. While the micelle was lodged inside the cell for an extended period of time with less than 3% released in two hours, the shell-crosslinked micelle quickly exited the OVCAR-3 cells (25% in two hours). For comparison, a small molecule (Lucifer yellow) was found to be only marginally faster than the crosslinked micelles (40% in 2 h). These results could have implications on the use polymer–drug conjugates or drug carriers where the drug needs to be released before the polymer undergoes exocytosis.
Starting Page	265
Ending Page	275
Page Count	11
File Format	HTM / HTML PDF
ISSN	20474830
Volume Number	1
Issue Number	3
Journal	Biomaterials Science
DOI	10.1039/c2bm00096b
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Clathrin Ether Caveolae Polymerization Micelle Poly(methyl methacrylate) Polymer Drug delivery Exocytosis Endocytosis Chain transfer Polyethylene glycol Carboxylic acid Lucifer yellow Copolymer
Content Type	Text
Resource Type	Article
Subject	Materials Science Biomedical Engineering

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