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

作者：Ji Liu, Luyin Liang, Ping Gan, Fanjie Lin, Zhiyue Dai, Zhangjing Chen, Yifan Xu, Qiuxing Yang, Mingyi Cao, Shiya Wang, Yueqing Gu, Zhenwei Yuan, Qifeng Zhong, Dejun Hu, Yongrong Yao · 发表于：Journal of Medicinal Chemistry · 年份：2025 · DOI：10.1021/acs.jmedchem.5c00066 · 被引用次数：20 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Nanoparticle-Based Drug Delivery

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 via 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.