• • CAMeO-Q NPs achieve synergistic low-temperature PTT by combining mitochondria-targeting photothermal agent and Hsp90 inhibitor, reversing thermal tolerance via ATP blockade and Hsp90 downregulation, with 660 nm laser irradiation inducing selective mitochondrial damage.
• • The nanoplatform enables trimodal imaging (FLI, PAI, PTI) for precise tumor localization and real-time therapy monitoring, addressing penetration depth limitations of single-modality imaging.
• • Homologous targeting enhances tumor accumulation and cellular uptake, improving therapeutic efficacy while minimizing off-target effects, as evidenced by in vivo melanoma models.
• • The energy disruptor strategy effectively inhibits heat shock protein expression, overcoming the major bottleneck of low-temperature PTT resistance, thereby increasing cancer cell death at lower temperatures and reducing collateral damage to normal tissues.