Development of a Nanotechnology Platform for Prostate Cancer Gene Therapy
Annual rept. 1 Jul 2011-30 Jun 2012
RUTGERS - THE STATE UNIV NEW BRUNSWICK NJ
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The objective of this research is to design and develop a nanocarrier that is able to evade the immune system, circulate in the blood stream, find its target prostate cancer cells, and transfer therapeutic genes into prostate cancer cells efficiently. The gene carrier is composed of a histone H2A peptide to condense pDNA into nano-size particles, b a PC-3 specific targeting motif TM to target prostate cancer cells, c an endosomolytic motif to disrupt endosome membrane, and d a nuclear localization signal NLS to actively translocate pDNA towards the nucleus of cancer cells. The gene delivery system was synthesized in E.coli. The vector was then complexed with plasmid DNA pDNA to form stable nanoparticles with sizes below 100nm. The nanoparticles were used to deliver reporter genes pEGFP to target PC-3 prostate cancer cells and RWPE-1 normal epithelial prostate cells. The induction of immune response by the vector was studied in BALBc immune-competent mice. The results demonstrated that the gene delivery system is able to target and efficiently transfect PC-3 cancer cells with minimum cross-reactivity with normal epithelial prostate cells. An animal protocol was prepared and approved by IACUC and DOD ACURO. The immunogenicity studies showed that the vector does not induce production IgG or IgM after repeated systemic injection.
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- Medicine and Medical Research