Tumor microenvironment-responsive modular integrated nanocomposites for magnetically targeted and photothermal enhanced catalytic therapy

Achieving efficient integration of cancer diagnosis and therapy is of great significance to human health, but the construction of a multifunctional intelligent therapy system still faces great challenges. In this study, we report an integrated multifunctional nanocomposite constructed by a simple modular assembly technology. The nanocomposites are composed of three different nanomaterials: Fe₃O₄, Au, and NaErF₄:0.5%Tm@NaYF₄ upconversion nanoparticles (UCNPs). In this design, Fe₃O₄ nanoparticles have nanozyme effect of peroxidase-like activity, which can react with H₂O₂ in the tumor microenvironment to generate hydroxyl radicals. Because of its magnetic properties, it can help the nanocomposites to aggregate under the induction of magnetic fields. Au nanoparticles exhibit nanozyme effect of glucose oxidase-like activity. It can catalyze the conversion of glucose to gluconic acid and H₂O₂. Ingeniously, the generated H₂O₂ provides a source of reactants for the reaction of the Fe₃O₄ nanozyme. In addition, the photothermal effect of Au nanoparticles under 808 nm irradiation further enhanced the nanozyme activity of Fe₃O₄ and Au nanoparticles. Besides, UCNPs can emit near-infrared (NIR)-II fluorescence under 808 nm irradiation, which can provide imaging-guided during cancer treatment. Then, the nanocomposites were further modified by poly(vinylpyrrolidone) (PVP) to obtain UCNPs/Au/Fe₃O₄-PVP with good biocompatibility and high-efficiency cancer treatment ability.