IDIC‐Based Phototheranostic Nanoparticles for NIR Light‐Excited Immuno‐Phototherapy

ABSTRACT The development of single component, multifunctional phototheranostic platforms remains a crucial objective in precision cancer therapy. Here, we design near‐infrared (NIR) light‐activated nanoparticles (NPs) by assembling IDIC with DSPE‐PEG‐NH 2 to achieve high photothermal conversion efficiency, reactive oxygen species generation, and biocompatibility. The resulting IDIC NPs exhibit strong NIR absorption and fluorescence, high photostability, and good aqueous stability. Upon 635‐nm laser irradiation, they reach a photothermal conversion efficiency of 52.8% and a singlet oxygen quantum yield of 43.0%, enabling synergistic photothermal and photodynamic therapy. In vitro, IDIC NPs show negligible dark toxicity but induce potent tumor cell ablation upon irradiation through mitochondrial membrane disruption and immunogenic cell death, evidenced by calreticulin exposure, HMGB1 release, and ATP secretion. In vivo, they enable effective NIR imaging, inhibit tumor growth, prolong survival, and cause minimal systemic toxicity. Laser‐treated tumors exhibit enhanced apoptosis, reduced proliferation, and macrophage polarization toward an M1 phenotype. These findings establish IDIC NPs as a robust, single‐component nanotheranostic agent integrating NIR imaging, photothermal/photodynamic synergy, and immune activation for cancer treatment.