Palladium-based multifunctional nanoparticles for combined chemodynamic/photothermal and calcium overload therapy of tumors

Due to the high mortality and incidence rates associated with tumors and the specificity of the tumor microenvironment (TME), it is difficult to achieve a complete cure for tumors using a single therapy. In this study, calcium carbonate-modified palladium hydride nanoparticles (PdH@CaCO3) were prepared and utilized for the combined treatment of tumors through chemodynamic therapy (CDT)/photothermal therapy (PTT) and calcium overload therapy. After entering tumor cells, PdH@CaCO3 releases calcium ions (Ca2+) and PdH once it reaches the TME due to the pH reactivity of the calcium carbonate coating. The mitochondrial membrane potential is lowered by the Ca2+, leading to irreversible cell damage. Meanwhile, PdH reacts with excessive hydrogen peroxide (H2O2) in the TME via the Fenton reaction, generating hydroxyl radicals (·OH). Moreover, PdH is an excellent photothermal agent that can kill tumor cells under laser irradiation, leading to significant anti-tumor effects. In vitro and in vivo studies have demonstrated that PdH@CaCO3 could combine CDT/PTT and calcium overload therapy, exhibiting great clinical potential in the treatment of tumors.