“Reactive oxygen species (ROS) engineering” is one of the most promising anti-tumor treatments developed in recent years. Massive explosion of ROS will cause oxidative stress, thereby inducing tumor cell death. However, ROS accumulation in tumor cells is eliminated by endogenous cellular self-regulation strategies. In this work, a kind of endogenous/exogenous dual stimulation nanoagent noted as UMZC is developed. Fenton reaction occurs between NH₂-MIL-88B(Fe) contained in UMZC and the overexpression of endogenous H₂O₂ to generate ROS, amplified by endogenous H₂S of colon tumor cells. In addition, NH₂-MIL-88B(Fe) also functions to deplete glutathione (GSH) for stopping it from consuming ROS. Upconversion nanoparticles at the core of UMZC convert near-infrared into visible light, which excites zinc phthalocyanine to initiate the photochemical reaction that generates more ROS, thus alleviating the lack of tissue penetration depth for visible light. Autophagy agonist chitosan oligosaccharides induce enhancement of cellular autophagy for disrupting cellular metabolic stress and the resistance to oxidative stress of tumor cells, allowing “ROS engineering” to fully exert anti-tumor effects. All of ROS generation, GSH depletion, and induced cellular autophagy caused by nanoagents have promoting effects on the occurrence of ferroptosis. Finally, the nanoagents show the ability to effectively treat colon tumors.

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.