A Single-Component Nanotheranostic Platform for Synchronous Cancer Imaging, Phototherapy, and Immune Activation

We constructed a single-component nanotheranostic platform by assembling IDIC-Phc6, a photosensitizer with an acceptor-donor-acceptor structure, with DSPE-PEG-NH₂. The IDIC-Phc6 nanoparticles (NPs) synchronized the following therapeutic and diagnostic functions upon single-wavelength excitation at 635 nm: (1) high-contrast tumor imaging through strong near-infrared (NIR) fluorescence emission, (2) localized hyperthermia due to high photothermal conversion efficiency (43.5%), and (3) activation of type I/II photodynamic therapy that generates both singlet oxygen (Φ_Δ = 48.7%) and superoxide anions to overcome tumor hypoxia. In vitro experiments confirmed the biocompatibility of IDIC-Phc6 NPs in the absence of photoactivation, whereas the combination of the NPs and laser irradiation induced apoptosis in tumor cells via mitochondrial membrane depolarization and triggered immunogenic cell death (ICD). Furthermore, IDIC-Phc6 NPs achieved precise tumor imaging in vivo through strong NIR fluorescence, significantly inhibited tumor growth via phototherapeutic effects, and remodeled the immune microenvironment. This single-component platform integrating theranostics, dual-modal synergistic therapy, and immune activation provides an innovative solution to overcome the barriers of the tumor microenvironment and enable clinical translation of precision phototherapy.