Magnetically navigated and PSMA/STEAP1 dual-targeted nanoliposomes for NIR-II/MRI imaging with photothermal-chemo-immunotherapy for prostate cancer

Precision theranostics for castration-resistant prostate cancer remain a major challenge because of tumor heterogeneity, drug toxicity, and resistance to conventional therapies. Here, we report a multifunctional theranostic nanoplatform that integrates multimodal imaging guidance, dual-targeted delivery, photothermal therapy, and immune activation for the precision treatment of prostate cancer. By encapsulating aggregation-induced emission luminogens and magnetic nanoparticles, this system achieves superior second near-infrared fluorescence and magnetic resonance imaging fusion for deep-tissue visualization. The dual-targeting strategy, which integrates magnetic navigation with simultaneous engagement of six-transmembrane epithelial antigen of the prostate 1 and prostate specific membrane antigen (PSMA), effectively addresses tumor heterogeneity by enabling externally guided and biologically specific delivery to both PSMA+ and PSMA− prostate cancer cells. Upon targeted delivery, the synergistic combination of photothermal therapy and chemotherapy achieves potent tumor growth inhibition, activates CD8+ T cells and macrophages to promote robust antitumor immune responses, and elicits durable immunological memory to prevent tumor recurrence. In vitro and in vivo studies demonstrate superior tumor targeting specificity, enhanced imaging contrast, and minimal off-target toxicity. This study provides novel insights into the construction of a multifunctional theranostic nanoplatform in precision oncology, with promising translational potential for clinical management of castration-resistant prostate cancer.