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J. Funct. Biomater. 2014, 5(3), 167-182; doi:10.3390/jfb5030167

Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles

1
Department of Biomedical Engineering, University of Michigan, 1101 Beal Ave., Ann Arbor, MI 48109, USA
2
Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109, USA
3
Macromolecular Science and Engineering Program, University of Michigan, 2300 Hayward Ave., Ann Arbor, MI 48109, USA
*
Author to whom correspondence should be addressed.
Received: 24 May 2014 / Revised: 26 July 2014 / Accepted: 28 July 2014 / Published: 16 September 2014
(This article belongs to the Special Issue Biomaterials Approaches for Cancer Research)
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Abstract

Short interfering RNA (siRNA) targeted against anti-apoptotic Bcl-2 protein proved to knockdown its expression and trigger cancer cell death. We used degradable, pH-sensitive, comb-like [P(EAA-co-BMA)-b-PNASI-g-P(HMA-co-TMAEMA)] polymer to condense anti-Bcl-2 siRNA into “smart” particles, which proved to shuttle their cargo past the endosomal membrane and into the cytoplasm of HeLa and UM-SCC-17B cancer cells. HeLa and UM-SCC-17B cancer cells were treated with anti-Bcl-2 particles followed by quantifying Bcl-2 mRNA and protein levels using qRT-PCR and western blotting, respectively. “Smart” anti-Bcl-2 particles selectively suppress Bcl-2 mRNA and protein levels in HeLa cells by 50%–60% and 79%–81%, respectively. Similarly, “smart” anti-Bcl-2 particles inhibited Bcl-2 mRNA levels by 30%, 40%, and 20% upon incubation with UM-SCC-17B cancer cells for 48, 72, and 96 h, respectively. Bcl-2 protein expression in UM-SCC-17B cancer cells was inhibited by 30% after treatment for 72 h. Results show that pH-sensitive comb-like polymer complex anti-Bcl-2 siRNA forming “smart” nanoparticles that deliver their cargo into the cytoplasm of HeLa and UM-SCC-17B cancer cells causing Bcl-2 knockdown at the mRNA and protein levels. View Full-Text
Keywords: pH-sensitive comb-like polymers; smart particles; endosomal escape; cytoplasmic siRNA delivery; Bcl-2 knockdown pH-sensitive comb-like polymers; smart particles; endosomal escape; cytoplasmic siRNA delivery; Bcl-2 knockdown
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MDPI and ACS Style

Lin, Y.-L.; Jiang, G.; Zhang, Z.; Nör, J.E.; ElSayed, M.E.H. Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles. J. Funct. Biomater. 2014, 5, 167-182.

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