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Journal of Drug Delivery
Volume 2012, Article ID 291219, 7 pages
Research Article

Triggered Rapid Degradation of Nanoparticles for Gene Delivery

1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, MC 0600 La Jolla, CA 92093-0657, USA
2Materials Science and Engineering Program, University of California at San Diego, 9500 Gilman Drive, MC 0600 La Jolla, CA 92093-0657, USA

Received 22 February 2012; Revised 1 May 2012; Accepted 4 May 2012

Academic Editor: Juan M. Irache

Copyright © 2012 José M. Morachis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Effective gene delivery tools offer the possibility of addressing multiple diseases; current strategies rely on viruses or polyplexes. Encapsulation of DNA within nanoparticles is an attractive alternative method for gene delivery. We investigated the use of our recently developed Logic Gate Nanoparticle for gene delivery. The nanoparticles, composed of a dual pH response random copolymer (poly-β-aminoester ketal-2), can undergo a two-step “in series” response to endosomal pH. The first sep is a hydrophobic-hydrophilic switch, which is followed immediately by rapid degradation. Rapid fragmentation is known to increase cytoplasmic delivery from nanoparticles. Therefore, we hypothesized that our Logic Gate Nanoparticles would enable increased gene delivery and expression relative to nanoparticles that degrade more slowly such as PLGA-based nanoparticles. Passive nanoparticle entry into cells was demonstrated by delivering Cy5-labeled pDNA encoding EGFP into HCT116, a colon carcinoma cell line. Flow cytometry analysis showed that cells are positive for Cy5-DNA-nanoparticles and produced EGFP expression superior to PLGA nanoparticles. Inhibition of V-ATPases using bafilomycin A1 demonstrates that expression of EGFP is dependent on low endosomal pH. The advanced Logic Gate Nanoparticles offer new therapeutic possibilities in gene delivery and other applications where rapid release is important.