Peptide functionalised nanoparticles for the selective induction of apoptosis in target cells

Anti-angiogenic therapies are practical strategies for the treatment of both obesity and cancer. The aim of this study was to develop gold nanoparticles (AuNPs) for targeted anti-angiogenic therapy. The objective was to... [ view full abstract ]

Anti-angiogenic therapies are practical strategies for the treatment of both obesity and cancer. The aim of this study was to develop gold nanoparticles (AuNPs) for targeted anti-angiogenic therapy. The objective was to develop AuNPs that can selectively deliver pro-apoptotic peptides to the endothelial cells of the vascular networks that supply the white adipose tissue (WAT), causing cell death and consequent reduction in the vasculature. Adipose Homing Peptide (AHP) binds to the prohibitin (PHB) which is over expressed on the surface of the endothelial cells in the WAT vasculature of obese individuals. 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. 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 expressing the receptor for AHP. The AuNPs induced significant levels of apoptosis Caco-2 cells, but not MCF7 and HT29 cells. 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.