Development of a Highly Efficient NIR-II Phototherapeutic Agent for Fluorescence Imaging-Guided Synergistic PTT/PDT/Chemotherapy of Colorectal Cancer

NIR-II-triggered phototherapy presents a noninvasive, resistance-free alternative therapeutic approach with deeper tissue penetration and improved imaging of deep tumors. However, many NIR-II phototherapeutic agents suffer from low fluorescence quantum yields, poor photothermal conversion efficiency (PCE), and reduced efficacy due to the upregulation of heat shock protein HSP70. This study develops a small-molecule NIR-II phototherapeutic agent (IRF) with a high fluorescence quantum yield (17.4%), excellent PCE (96.8%) for photothermal therapy (PTT), and photodynamic therapy (PDT) activity. To decrease thermal resistance during phototherapy, IRF and evodiamine (EVO) were loaded onto hyaluronic acid (HA)-modified nanoparticles, creating a multifunctional nanoplatform termed EVO/IRF@HA NPs. EVO/IRF@HA NPs can actively target tumors for NIR-II fluorescence imaging <i>via</i> the HA moiety. Upon 980 nm laser irradiation, IRF increases the temperature and content of reactive oxygen species for synergistic PTT/PDT. Importantly, EVO effectively inhibits the overexpression of HSP70, enabling combined PTT/PDT/chemotherapy for effective colorectal cancer (CRC) treatment.