Defect-engineered Fe3O4@SnO2 nanozyme microneedles couple local photothermal-photodynamic therapy with redox-amplified ferroptosis

Abstract

Localized nanocatalytic therapy is constrained by insufficient reactive oxygen species (ROS) output, tumor antioxidant buffering, and poor retention of therapeutic agents at the lesion. Here, we report an oxygen-deficient Fe 3 O 4 @SnO 2 nanozyme (HFC) co-delivered with gallic acid (GA) through dissolving poly(sodium acrylate)/poly(vinyl alcohol)/poly(vinylpyrrolidone) microneedles (HFCG-MN). Hollow-structure formation and stepwise calcination increased the oxygen-vacancy signal, broadened optical absorption, and lowered interfacial charge-transfer resistance. Under 655 nm irradiation, HFC produced stable, power-dependent heating together with singlet oxygen and hydroxyl radicals, while depleting approximately half of the available glutathione within 120 min. The PAAs/PVA/PVP matrix provided mechanically robust skin penetration, rapid dissolution, and acid- and light-responsive GA release. In 4T1 cells, the combined treatment generated the strongest ROS signal, disrupted lysosomal and mitochondrial homeostasis, increased intracellular Fe 2+ and lipid peroxidation, and caused extensive cell death. In a 4T1 tumor model, HFCG-MN plus laser irradiation increased the local tumor temperature to approximately 55 °C within 10 min and restricted the mean tumor volume to 101.2 mm 3 on day 14, compared with 871.7 mm 3 in the control group, corresponding to a tumor-inhibition rate of 88.4%. No evident body-weight loss or major-organ histopathology was observed. These data support a local therapeutic platform that couples defect-engineered nanozyme chemistry and microneedle delivery with photothermal/photodynamic action and redox-amplified ferroptosis-associated damage.