Executive Summary : | Advances in nanotechnology have the potential to combat undesirable outcomes in cancer therapy, particularly nanogold-based treatments. However, off-target accumulation and biodegradation issues limit its clinical application. To address these limitations, a novel approach is proposed: biomineralization of cancer cells using ionic gold-laden carriers for intracellular nanogold generation for photothermal cancer therapy. This involves harnessing mitochondrial pH, a physiological factor that influences the bioreduction of ionic gold mediated by polyphenol components of nanovectors. This approach provides adequate nanogold concentration in a short time from therapeutically relevant low doses of ionic gold at the target site for desired activity under appropriate photothermal therapy regimens. These nanocarriers also carry anticancer therapeutic molecules at sub-cytotoxic concentrations, achieving synergistic outcomes in a combinatorial chemophotothermal treatment strategy. Mitochondrial targeting functional nanocarriers will be fabricated using bioconjugates of triphenylphosphonium cation, polyethylene glycol polymers, and polyphenols. The drug and ionic gold-laden nanocarriers will be thoroughly characterized and evaluated for their potential intramitochondrial bioreduction using UV-Vis, HR-TEM, XPs, and ICP-Ms tools. The feasibility of this novel approach will be demonstrated through tumor treatment and assessment of clearance and biodistribution of organic nanocarriers in animal models. |