Optimization of fabrication parameters to produce chitosan-TripolyphosphateNanoparticles for P53 gene delivery

摘要

Safe, efficient, and specific delivery oftherapeutic genes remains an importantbottleneck for the development of genetherapy. Novel biocompatible polymeric genecarriers have been examined for their potentialin treating various genetic and acquireddiseases. Inefficient endosomal release,cytoplasmic transport, and nuclear entry ofplasmids are currently limiting factors in theuse of polymers for effective plasmid- basedgene therapy [1]. Therefore, several differentpolymeric gene carriers have been designedrecently in an attempt to overcome theseproblems. Biocompatibility, lowimmunogenicity and minimal Cytotoxicity canrender such polymers a good alternative toviral or lipid mediated transfection. Chitosan isa cheap, biocompatible, biodegradable andnon-toxic cationic polymer that formspolyelectrolyte complexes with DNA [2]. Thep53 tumor suppressor gene, which is the focusof this paper, has been a major player innumerous gene therapy studies concerning thetreatment of cancer. The p53 tumor suppressorhas been implicated in more than 50% ofhuman cancers [3]. The p53 protein is DNAbindingand acts as a transcription factor tocontrol the expression of proteins involved inthe cell cycle [4]. In response to DNA damage,p53 accumulates in the cell nucleus, whichcauses cells to undergo cell cycle arrest andDNA repair or apoptosis. [5]. In this study, wehave determined the antiproliferative activityof wild-type (wt) p53 gene loadednanoparticles in a cancer cell line.