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Nanocarrier Cross-Linking Density and pH Sensitivity Regulate Intracellular
 

Summary: Nanocarrier Cross-Linking Density and
pH Sensitivity Regulate Intracellular
Gene Transfer
Jin-Oh You and Debra T. Auguste*
School of Engineering and Applied Sciences, HarVard UniVersity,
Cambridge, Massachusetts 02138
Received August 25, 2009; Revised Manuscript Received October 5, 2009
ABSTRACT
Treatment of diseases on the molecular level by genetic material is limited by effective delivery mechanisms. We focused on the synthesis
of a pH-sensitive gene delivery vehicle based on dimethylaminoethyl methacrylate (DMAEMA) with tunable swelling, cross-linking density, and
DNA release kinetics within the endosomal pH range. Our strategy, which utilized a single step for DNA encapsulation, enhanced gene transfection
efficiency and reduced cytotoxicity relative to polyethyleneimine (PEI) and poly-L-lysine (PLL).
The acidic endosomal compartment (pH 5-61,2
from
early to late endosome) has been exploited in several drug
and gene delivery applications.3-7
PLL, PEI, and DMAEMA
have been used extensively due to their high transfection
efficiencies, but cytotoxicity often limits their clinical
use.8,9

  

Source: Auguste, Debra T. - School of Engineering and Applied Sciences, Harvard University

 

Collections: Materials Science; Biology and Medicine