Pluronic F127 engineered nanotheranostics for NIR-II fluorescence imaging and enhanced photodynamic therapy in melanoma.

Conventional photosensitizers (PSs) are hindered by aggregation-caused quenching, limited tissue-penetration depth and off-target toxicity, which restricts their clinical translation for photodynamic therapy (PDT). To tackle these bottlenecks, we constructed an all-in-one nanotheranostic system named F127@546, where a donor-acceptor-type fluorophore (IR-546) with twisted intramolecular charge-transfer (TICT) characteristics is encapsulated within the amphiphilic polymer Pluronic F127. This rational design not only substantially improves biocompatibility but also induces a prominent emission red shift from 605 nm to 900 nm, with an emission tail extending above 1000 nm to realize high-resolution deep-tissue NIR-II imaging. Beyond its NIR-II imaging capability, F127@546 acts as an effective dual-mode photosensitizer upon 660 nm laser irradiation to concurrently produce type-I and type-II reactive oxygen species (ROS). The generated ROS dissipates mitochondrial membrane potential and further initiates melanoma cell apoptosis. In vivo experiments were performed via intratumoral injection of F127@546. We verified that its photodynamic therapy exerted a remarkable inhibitory effect on tumors, accompanied by negligible systemic toxicity. This study provides a generalizable blueprint for fabricating multifunctional nanoplatforms that combine deep tissue imaging and synergistic photodynamic therapy, advancing the development of precision-oriented anti-tumor treatment.