Corrosion‐Activated Chemotherapeutic Function of Nanoparticulate Platinum as a Cisplatin Resistance‐Overcoming Prodrug with Limited Autophagy Induction

Despite nanoparticulate platinum (nano‐Pt) has been validated to be acting as a platinum‐based prodrug for anticancer therapy, the key factor in controlling its cytotoxicity remains to be clarified. In this study, it is found that the corrosion susceptibility of nano‐Pt can be triggered by inducing the oxidization of superficial Pt atoms, which can kill both cisplatin‐sensitive/resistance cancer cells. Direct evidence in the oxidization of superficial Pt atoms is validated to observe the formation of platinum oxides by X‐ray absorption spectroscopy. The cytotoxicity is originated from the dissolution of nano‐Pt followed by the release of highly toxic Pt ions during the corrosion process. Additionally, the limiting autophagy induction by nano‐Pt might prevent cancer cells from acquiring autophagy‐related drug resistance. With such advantages, the possibility of further autophagy‐related drug resistance could be substantially reduced or even eliminated in cancer cells treated with nano‐Pt. Moreover, nano‐Pt is demonstrated to kill cisplatin‐resistant cancer cells not only by inducing apoptosis but also by inducing necrosis for pro‐inflammatory/inflammatory responses. Thus, nano‐Pt treatment might bring additional therapeutic benefits by regulating immunological responses in tumor microenvironment. These findings support the idea that utilizing nano‐Pt for its cytotoxic effects might potentially benefit patients with cisplatin resistance in clinical chemotherapy.