Title : Peptide functionalized nanoparticles for the selective induction of apoptosis in target cells
The unique optical properties of gold nanoparticles (AuNP) can facilitate the development of ultrasensitive imaging-based therapeutic systems. Several studies have demonstrated the application of AuNPs for targeted drug delivery and photothermal therapy (PTT). Consequently, a number of gold nanoparticle-based therapies are currently in clinical trials. In this study we demonstrate the application of AuNPs as multimodal drug delivery systems for the targeted destruction of cells as a treatment for obesity. The multimodal functionality of the AuNPs was achieved by conjugating the AuNPs with two peptides, a pro-apoptotic therapeutic peptide and a receptor targeting peptide. Prohibitin (PHB) is a multifunctional protein, which is over expressed on the surface of the endothelial cells in the White Adipose Tissue (WAT) vasculature of obese individuals. Adipose Homing Peptide (AHP) is a PHB targeting peptide that binds to PHB with high specificity. We previously demonstrated that AuNPs functionalized with AHP accumulated in the WAT of animal models of obesity. We evaluated the selective targeting and toxicity of AuNPs that were bi-functionalised with AHP and a pro-apoptotic peptide (KLAKLAK). We used 3 human cancer cell lines (Caco-2, MCF7 and HT29), of which only one (Caco-2) express PHB. Toxicity was evaluated using the WST-1 and the APOPercentage assays, while the uptake of the nanoparticles was confirmed by ICP-OES and TEM analysis. The cytotoxic activity of the receptor targeted AuNPs was more pronounced in the cells ex-pressing the receptor for AHP. The AuNPs induced significant levels of apoptosis Caco-2 cells, but not MCF7 and HT29 cells. We applied these AuNPs in an animal study and demonstrated anti-obesity effects, which resulted in reduced body weight and reduced adipose tissue mass. This study shows receptor mediated targeting, and the selective destruction of cells expressing the receptor through the induction of apoptosis and the potential for the development of targeted anti-angiogenic strategy.
Audience take away:
• My presentation will focus on design and application of multimodal drug delivery systems, peptide targeted drug delivery and the therapeutic potential of gold nanoparticles. It will describe preclinical in vitro and in vivo research towards a treatment for obesity.