Enzyme-based anticancer therapy is more attractive for the less side effect than conventional chemotherapy. However, the poor stability and low membrane permeability of enzymes during the intracellular delivery are constraints for its practical applications. In this work, we synthesized novel near-infrared (NIR)-responsive core–shell-structured Prussian blue@fibrous SiO₂ (PBFS) nanoparticles as the carrier of superoxide dismutase (SOD) and a glutathione (GSH)-activated Fenton reagent (DiFe). The PBFS nanoparticles are further modified with a GSH-responsive cationic polymer (poly(2-(acryloyloxy)-N, N-dimethyl-N-(4-(((2-((2-(((4-methyl-2-oxo-2H-chromen-7-yl)carbamoyl)oxy)ethyl)disulfaneyl)ethoxy)carbonyl)amino)benzyl)ethan-1-aminium, PSS) containing disulfide bonds and fluorophores. After SOD and DiFe are loaded on the PBFS-PSS nanoparticles, dual chemodynamic/photothermal therapeutic nanoparticulate systems (PBFS-PSS/DiFe/SOD) are obtained. In vitro experiments show that PBFS-PSS/DiFe/SOD nanoparticles have good biocompatibility and can be tracked under fluorescence microscope during the intracellular delivery process in MCF-7 tumor cells due to the GSH-activated release of fluorophores. They also exhibit high efficiency in NIR photothermal conversion and GSH-activated Fenton reaction in tumor cells, thus achieving high-efficient killing effect of tumor cells based on the combination of photothermal and chemodynamic therapeutic performance (PTT and CDT). This work offers a novel pathway to construct a visual multifunctional nanomedicine platform for future cancer therapy.

Recent advances in the research on the molecular mechanism of cell death and methods for preparation of nanomaterials make the integration of various therapeutic approaches, targeting, and imaging modes into a single nanoscale complex a new trend for the development of future nanotherapeutics. Hence, a novel ellipsoidal composite nanoplatform composed of a magnetic Fe₃O₄/Fe nanorod core (~120 nm) enwrapped by a catalase (CAT)-imprinted fibrous SiO₂/ polydopamine (F-SiO₂/PDA) shell with thickness 70 nm was prepared in this work. In vitro experiments showed that the Fe₃O₄/Fe@F-SiO₂/PDA nanoparticles can selectively inhibit the bioactivity of CAT in tumor cells by the molecular imprinting technique. As a result, the H₂O₂ level in tumor cells was elevated dramatically. At the same time, the Fe₃O₄/Fe core released Fe ions to catalyze the conversion of H₂O₂ to ·OH in tumor cells. Eventually, the concentration of ·OH in tumor cells rapidly rose to a lethal level thus triggering apoptosis. Combined with the remarkable near-infrared light (NIR) photothermal effect of the CAT- imprinted PDA layer, the Fe₃O₄/Fe@F-SiO₂/PDA nanoparticles can effectively kill MCF-7, HeLa, and 293T tumor cells but are not toxic to nontumor cells. Furthermore, these nanoparticles show good capacity for magnetic targeting and suitability for magnetic resonance imaging (MRI). Therefore, the integrated multifunctional nanoplatform opens up new possibilities for high-efficiency visual targeted nonchemo therapy for cancer.