Temperature and Tumor Microenvironment Dual Responsive Mesoporous Magnetic Nanospheres for Magnetothermal Effect-Induced Cancer Theranostics

The development of smart drug delivery systems (SDDSs) based on engineered nanomaterials is important for clinical applications. Nevertheless, controllable administration of chemotherapeutic drugs for deep tumors and the avoidance of side effects caused by off-targeting during delivery remain a great challenge. Herein, a stimulus-responsive system of mesoporous nanospheres (composed of Cu@Fe2C@mSiO(2)) with good magnetothermal effect is introduced into the tumor microenvironment. This system plays an important role in image-guided controllable targeted drug delivery that is independent of tumor depth. Aggregation-induced emission luminogen-based fluorescence imaging and magnetic resonance imaging were utilized since these techniques visualize the delivery process in real time. In addition, the degraded nanocarriers showed high catalytic activity for Fenton and Fenton-like reactions, upregulating the level of hydroxyl radicals (center dot OH) in cancer cells to realize chemodynamic therapy. The induced center dot OH led to the overexpression of pho-STAT3, activating the STAT3 signaling pathway, eventually inducing cancer cell apoptosis. Through metabolic monitoring, this SDDS is removed from the body after its degradation in vivo. The synergistically enhanced therapeutic effect was obtained in the chemo-chemodynamic therapy of 4T1 tumor-bearing mice, offering a platform for efficient cancer therapy with a personalized theranostic strategy.