Discovery of a Monoiodo Aza-BODIPY Near-Infrared Photosensitizer: in vitro and in vivo Evaluation for Photodynamic Therapy.

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 .