Restoration of p53 Function in Ovarian Cancer Mediated by Gold Nanoparticle-Based EGFR Targeted Gene Delivery System

• Published in: ACS biomaterials science & engineering 2019-07, Vol.5 (7), p.3631-3644
• Main Authors: Kotcherlakota, Rajesh, Vydiam, Kalyan, Jeyalakshmi Srinivasan, Durga, Mukherjee, Sudip, Roy, Arpita, Kuncha, Madhusudana, Rao, T. Nageswara, Sistla, Ramakrishna, Gopal, Vijaya, Patra, Chitta Ranjan
• Format: Article
• Language: English
• ISSN: 2373-9878; 2373-9878
• DOI: 10.1021/acsbiomaterials.9b00006

Targeted gene delivery of wild type tumor suppressor gene p53 is a promising approach to inhibit the progression of ovarian cancer. Although several gene delivery vehicles have been reported earlier, there is paucity for targeted delivery of wild type p53 to ovarian cancer using gold nanoparticles. As it is well-known that EGFR (epidermal growth factor receptor) is overexpressed in ovarian cancer, in this study we hypothesized that the FDA approved monoclonal antibody C225 (cetuximab) that targets EGFR could be used for targeted delivery of wild type p53 gene. With this impetus, we devised an approach wherein cationic gold nanoparticles (AuNPs) were employed to generate gold nanoparticle-based drug delivery system (DDS, Au-C225-p53DNA where p53DNA is pCMVp53 plasmid) that was formulated and characterized by biochemical and biophysical methods. The nanoconjugate complexed with DNA (Au-C225-p53DNA) is serum-stable and protects the bound DNA from digestion by DNase-I. Additionally, in vitro reporter gene expression assays demonstrated efficient and specific gene transfection in EGFR overexpressing SK-OV-3 cells. Further, the intraperitoneal administration of Au-C225-p53DNA in SK-OV-3 xenograft mouse model displayed significant tumor targeting and tumor regression. Altogether, these studies indicated a promising nanoparticle-based approach for targeting ovarian cancers caused by mutated p53.