Therapy-chemotherapy dual mode intelligent nano hydrogen generator for tumor treatment

Prodrugs enable targeted and precise release through chemical modifications, optimizing pharmacokinetics, minimizing side effects, and enhancing therapeutic efficacy, making them a powerful tool in precision medicine. However, prodrug activation systems face clinical translation challenges, such as off-target activation, metabolic variability, and imprecise external triggering, which reduce therapeutic precision and limit their clinical potential. Here, we have designed an engineering graphene oxide (GO)/Ba 0.85 Ca 0.15 Zr 0.1 Ti 0.9 O₃ (BCZT/GO) energy nanoconverter, which can achieve precise prodrug resurgence through precise external ultrasound triggering. The system initiates the proton sponge effect via the transformation of a pH-responsive structure, which disrupts the integrity of the lysosomal membrane and facilitates the escape of nanoparticles from lysosomal entrapment. Upon ultrasound (US) irradiation in the acidic tumor microenvironment (TME), BCZT/GO generates hydrogen (H 2 ), converting the Pt (IV) prodrug into a bioactive Pt (II) compound. This catalytic transformation results in the formation of cytotoxic DNA-cisplatin cross-links, thereby inhibiting DNA replication and repair in cancer cells and significantly suppressing tumor growth in tumor-bearing mouse models. This gas reduction strategy demonstrates that ultrasonically activated piezoelectric materials can serve as an effective mechanism for precise drug delivery and controlled release. This innovative approach holds great promise for the treatment of advanced cancer and provides a versatile platform for targeted therapeutic interventions.