Development of a Nanotechnology Platform for Prostate Cancer Gene Therapy
Abstract
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 BALB/c 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA581408
Entities
People
- Arash Hatefi
Organizations
- Rutgers University–New Brunswick