Attenuating chemotherapy-induced nephrotoxicity while potentiating antitumor efficacy by transforming a Janus drug into dual-targeting carbonized polymer dots.

Abstract

Chemotherapy-induced acute kidney injury (AKI) remains a major clinical challenge because existing renoprotective agents often compromise the antitumor efficacy of chemotherapeutics. To address this limitation, we transformed apigenin, a natural flavonoid with Janus bioactivities, into bioactive carbonized polymer dots (Api-CPDs) via a one-step carbonization process. The resulting Api-CPDs exhibit markedly high hydrophilicity, prolonged retention in the body, and, most importantly, preferential accumulation in both renal tissues and tumors. Mechanistically, Api-CPDs potently activate the Nrf2/HO-1 pathway and promote mitophagy, thereby shielding kidneys from cisplatin-induced apoptosis. Beyond conferring renoprotection, Api-CPDs enhance the antitumor efficacy of chemotherapeutics by modulating the p53 pathway. Collectively, this study demonstrates that transforming a Janus drug into bioactive carbonized polymer dots effectively overcomes the inherent limitations of small-molecule flavonoids, including poor aqueous solubility, rapid clearance, and lack of target specificity, enabling concurrent mitigation of chemotherapy-induced nephrotoxicity and potentiation of antitumor efficacy.