Size-based Optimization of P53 gene-loaded Chitosan Nanoparticles

Safe, efficient, and specific delivery of therapeutic genes remains an important bottleneck for the development of gene therapy. Novel biocompatible polymeric gene carriers have been examined for their potential in treating various genetic and acquired diseases. Inefficient endosomal release, cytoplasmic transport, and nuclear entry of plasmids are currently limiting factors in the use of polymers for effective plasmid-based gene therapy [1]. Therefore, several different polymeric gene carriers have been designed recently in an attempt to overcome these problems. Biocompatibility, low immunogenicity and minimal cytotoxicity can render such polymers a good alternative to viral or lipid mediated transfection. Chitosan is a cheap, biocompatible, biodegradable and non-toxic cationic polymer that forms polyelectrolyte complexes with DNA [2]. The p53 tumor suppressor gene, which is the focus of this paper, has been a major player in numerous gene therapy studies concerning the treatment of cancer. The p53 tumor suppressor has been implicated in more than 50% of human cancers [3]. The p53 protein is DNA-binding and acts as a transcription factor to control the expression of proteins involved in the cell cycle [4]. In response to DNA damage, p53 accumulates in the cell nucleus, which causes cells to undergo cell cycle arrest and DNA repair or apoptosis. [5]. in this study, we have determined the antiproliferative activity of wild-type (wt) p53 gene-loaded nanoparticles in a cancer cell line