Porous Fe/Cu Nanoreactor with Dual Insurance Design for Precision Chemotherapy and Chemodynamic Therapy.

Abstract

Poor prognosis and chemotherapy response stem from difficulties in precise targeting and the lack of effective synergistic treatments. Nanozymes show promising potential in tumor chemodynamic therapy (CDT) by catalyzing hydrogen peroxide (H₂O₂) decomposition and glutathione depletion in the tumor microenvironment (TME). However, integrating precise chemotherapy targeting with CDT remains challenging. In this study, a porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) is developed for co-loading with the humanized 3F8 anti-GD2 disialoganglioside antibody (3F8) and the novel pyridazinone-based chemotherapeutic agent (IMB), forming a nanoreactor (3F8@FeCuNPs@IMB) for targeted chemotherapy and CDT. The nanoreactor responds specifically to the acidic TME as a primary insurance, allowing for the controlled release of IMB at the tumor site. The targeting antibody 3F8 coating on the surface of the nanozyme carrier acts as a secondary insurance, minimizing chemotherapy drug leakage during the delivery process and ensuring precise targeting for effective chemotherapy. Furthermore, FeCuNPs act as peroxidase-like (POD) and glutathione oxidase-like (GSHOX) enzymes, catalyzing hydroxyl radical (•OH) generation and depleting excess GSH, enhancing CDT. The results in vitro and in vivo indicate that the dual insurance designed 3F8@FeCuNPs@IMB offers a promising prospect for a targeted, precise, and effective combination of chemotherapy and CDT against melanoma.