School of Pharmacy, Fudan University, Shanghai 201203, P. R. China.
Shanghai Skin Disease Hospital, Shanghai 200443, P. R. China.
J Med Chem. 2020 Sep 10;63(17):9950-9964. doi: 10.1021/acs.jmedchem.0c00882. Epub 2020 Aug 25.
Photodynamic therapy (PDT) as a rising platform of the cancer treatment method is receiving increased attention. Through systematic evaluation of halogen substitution on aza-4,4-difluoro-4-bora-3,4-diaza--indacenes (BODIPY), we have found that monoiodo-derived aza-BODIPYs provided greater efficacy than other halogenated aza-BODIPY PSs. and as monoiodinated aza-BODIPY dyes containing -methoxyphenyl moiety were identified to be potent NIR aza-BODIPY-type PSs with IC values against HeLa cells at a light dose of 54 J/cm as low as 76 and 81 nM, respectively. possessed superior phototoxicity, low dark toxicity, and good thermal/photostability and distributed majorly in mitochondria in cells. Apoptosis was verified to be the main cell death pathway, and in vitro reactive oxygen species generation was demonstrated. In vivo whole-body fluorescence imaging and ex vivo organ distribution studies suggested that afforded an excellent PDT effect with a low drug dose under single-time light irradiation and revealed advantages over known PSs of and .
光动力疗法（PDT）作为一种新兴的癌症治疗方法，受到了越来越多的关注。通过对氮杂-4,4-二氟-4-硼-3,4-二氮杂-茚（BODIPY）上卤素取代的系统评价，我们发现单碘取代的氮杂 BODIPY 比其他卤代氮杂 BODIPY PS 具有更高的疗效。其中，含有 -甲氧基苯基部分的单碘代氮杂 BODIPY 染料被鉴定为具有强大的近红外氮杂 BODIPY 型 PS，在光剂量为 54 J/cm 时，对 HeLa 细胞的 IC 值低至 76 和 81 nM。与已知的 PS 相比，具有优越的光毒性、低暗毒性、良好的热/光稳定性，并且主要分布在细胞的线粒体中。凋亡被证实是主要的细胞死亡途径，并且在体外证明了活性氧的产生。体内全身荧光成像和离体器官分布研究表明，在单次光照射下，低剂量药物即可实现优异的 PDT 效果，并显示出优于已知 PS 和 的优势。
