Visualized self-propelled nanorobots overcome tumor barriers for boosted photothermal-nanocatalytic synergistic therapy against triple-negative breast cancer

Abstract

Conventional nanozyme-based therapeutics for triple-negative breast cancer (TNBC) are severely hindered by insufficient tumor penetration and lysosomal degradation-induced enzyme inactivation, crippling therapeutic efficacy. Herein, we rationally construct visualized dual-propelled Janus PDAPdAu nanorobots (PPA NBs) with cascade catalytic activity for synergistic photothermal-nanocatalytic therapy of TNBC. Powered by near-infrared light-triggered thermophoresis and nanozyme-fueled oxygen propulsion, PPA NBs realize deep tumor penetration and lysosomal escape. PPA NBs exhibit catalase-mimicking activity to alleviate tumor hypoxia through hydrogen peroxide decomposition, and glucose oxidase-mimicking activity to deplete glucose and downregulate heat shock proteins, thus sensitizing TNBC to photothermal therapy (PTT). Localized hyperthermia further enhances nanozyme catalysis, forming an amplified synergy between nanocatalytic therapy and PTT that affords an outstanding 97% tumor inhibition rate. Furthermore, PPA NBs act as excellent fluorescent biosensing probes for visual lesion localization. Overall, this work provides visual diagnosis and advanced TNBC phototherapy strategies, a reliable paradigm for cancer patients’ health monitoring and treatment.