CuS-based nanoplatform for NIR-II photothermal-enhanced and celastrol-boosted cuproptosis in prostate cancer

Cuproptosis-based therapy has emerged as a promising strategy for cancer treatment, but its efficacy is limited by insufficient copper accumulation and poor therapeutic specificity. Herein, we developed a multifunctional CuS@Cel/PCM-MPNs nanoplatform for synergistic prostate cancer theranostics by integrating the second near-infrared (NIR-II) photothermal therapy, responsive drug release, and dual-modal photoacoustic/magnetic resonance imaging. Hollow CuS nanoparticles were used for celastrol (Cel) loading and further modified with phase change material (PCM) and Mn²⁺-tannic acid metal-polyphenol networks (MPNs). Under acidic and photothermal conditions, the nanosystem enabled responsive release of Cu ions and Cel, leading to amplified oxidative stress and enhanced cuproptosis in tumor cells. Meanwhile, the nanoplatform exhibited excellent photothermal performance under 1064 nm laser irradiation and effective photoacoustic (PA)/magnetic resonance (MR) imaging capability. Both in vitro and in vivo studies demonstrated efficient tumor accumulation, significant antitumor efficacy against RM1 prostate tumors, and favorable biosafety. Overall, this work provides a promising strategy for synergistic photothermal and cuproptosis-based therapy for precise prostate cancer treatment.