Multifunctional mitochondria-targeting energy disruptor for enhancing imaging-guided low-temperature photothermal therapy of melanoma
The evolution of precision medicine has propelled multimodal imaging-guided phototheranostics to the forefront for precise tumor diagnosis and therapy. Low-temperature photothermal therapy (PTT) offers a promising approach for the treatment of melanoma due to its non-invasiveness and minimal damage to normal tissues. However, its efficacy is limited by cancer cell thermal tolerance. To address this, a new type of multifunctional energy disruptor (CAMeO-Q NPs) is developed featuring homologous targeting and mitochondria targeting, and synergistically enhancing low-temperature PTT in melanoma by reversing heat shock protein 90 (Hsp90)-mediated thermal tolerance and blocking mitochondrial adenosine triphosphate (ATP) biosynthesis. The multifunctional energy disruptor enables precise trimodal imaging (fluorescence imaging/FLI, photoacoustic imaging/PAI, and photothermal imaging/PTI) guidance for low-temperature PTT. Comprising a mitochondria-targeting photothermal agent and an Hsp90 inhibitor, CAMeO-Q NPs induce selective mitochondrial damage under 660 nm laser irradiation and downregulate cellular HSP expression by ATP inhibition and Hsp90 inhibitor. This multifunctional energy disruptor provides a novel strategy for enhancing multimodal imaging-guided low-temperature photothermal therapy through combined homologous targeting, mitochondria-targeting, and Hsp90 inhibition.