Executive Summary : | The project aims to develop a CD44-targeted silica nanocarrier with polydiacetylene coating to deliver metallodrugs that face challenges in phase trials, rejected during clinical trials, and other metal complexes under preclinical evaluation. The non-fluorescent and non-responsive conventional silica nanocarrier can be modified into a fluorogenic and stimuli-responsive smart nanocarrier due to the polydiacetylene coating. The project also aims to investigate the molecular mechanism of cancer growth inhibition through the endoplasmic reticulum stress pathway and evaluate tumor-targeting efficacy using bioimaging in a mouse breast cancer xenograft model. The evaluation of in vitro and in vivo stability, release profile, and pharmacokinetic and pharmacological properties of nanocomposite-containing metallodrugs towards the breast tumor microenvironment could provide an immediate clinical impact in breast cancer therapy. This approach could help overcome the limitations of metal toxicity, low target selectivity, poor stability in the physiological environment, rapid renal clearance, and multi-faceted modes of action in metal complexes. |