Fe-POM Anchored on mSiO₂-Coated Upconversion Nanoparticles for Cascading Catalytic Nano-Synergistic Therapy

Traditional tumor treatments have limitations, such as poor targeting and systemic toxicity. Therefore, the development of intelligent nanotheranostic systems is necessary. In this work, we developed a multifunctional core-shell nanocomposite named upconversion nanoparticles (UCNPs) coated with mesoporous silica and anchored with Fe-substituted polyoxometalate (UCNPs@mSiO₂/Fe-POM). This system uses UCNPs as the core for imaging. The core is encapsulated within a mesoporous silica (mSiO₂) shell. This shell contains Fe-substituted polyoxometalate (POM, Fe-POM), in which Fe ions are incorporated into the POM framework to introduce redox-active catalytic sites, enabling efficient light-to-heat conversion. Consequently, this platform integrates computed tomography imaging with photothermal therapy (PTT) and chemodynamic therapy (CDT). Under 808 nm laser irradiation, Fe-POM acts as a photothermal agent for PTT. At the same time, it initiates Fenton-like reactions to generate cytotoxic hydroxyl radicals (·OH) for CDT. During this process, Fe²⁺ and Mo⁵⁺ oxidize to Fe³⁺ and Mo⁶⁺. Then, these ions react with intracellular glutathione (GSH). This converts GSH to glutathione disulfide (GSSG) while reducing the ions back to Fe²⁺ and Mo⁵⁺. This process maintains the reaction cycle. This continuous cycling occurs in the tumor microenvironment and consumes intracellular GSH. Due to this consumption, the tumor's antioxidant defense weakens. Thus, the therapeutic effect of CDT increases. This strategy, combined with the imaging capability of UCNPs, demonstrates excellent antitumor performance.