Diradical-Featured N-Arene Croconaine-Based Nanoagent for Synergistic Photodynamic/Photothermal Tumor Therapy

Abstract

Organic radical materials with narrow bandgaps and small singlet-triplet energy gaps are ideal for synergistic photodynamic/photothermal therapy (PDT/PTT), but suffer from their poor stability. Croconaines (CRs), resonance-stabilized zwitterionic donor-acceptor-donor π-conjugated compounds with diradical character and good stability, mostly follow the energy gap law, undergoing ultrafast internal conversion to the ground state, thus being mainly used for PTT with rare PDT or synergistic PDT/PTT exploration. Inspired by recent advances in N-arene CRs with efficient coupling of photothermal and photosensitizing effects, this work designs and synthesizes CR620, the first N-arene CR for synergistic PDT/PTT. Water-soluble CR620 nanoparticles (NPs) are prepared via nanoprecipitation. CR620 exhibits a strong absorption peak at 620 nm (ε = 5.05 × 10 4 L•mol -1 •cm -1 ) and good photostability. Under 660 nm laser irradiation, CR620shows efficient reactive oxygen species (ROS) generation and high photothermal conversion efficiency (PCE, 30.4% for CR620; 41.12% for CR620 NPs). In vitro and in vivo studies on 4T1 tumor models confirm that CR620 NPs synergistically inhibit tumor proliferation via ROS-mediated oxidative stress and thermal damage, achieving a tumor growth inhibition rate of 89% with favorable biocompatibility and safety. This work provides a new molecular design strategy for N-arene CR-based bifunctional phototherapeutic agents.