Aza-BODIPY nanomicelles as versatile agents for the in vitro and in vivo singlet oxygen-triggered apoptosis of human breast cancer cells.

Herein, we synthesised four aza-BODIPY dyes (1-4) with the singlet oxygen generation quantum yield values of ca. 65-85%. Furthermore, we formulated a nanomedicine by encapsulating these dyes into an amphiphilic micelle, DSPE. The spherical nanomicelles formed were characterized using photophysical and morphological analyses, and their in vitro and in vivo photodynamic efficacies were investigated. One of the conjugates, DSPE-1, showed the lowest IC value of 2 μM against a human breast cancer cell line (MDA MB 231). The mechanism of photodynamic activity has been evaluated by employing different biophysical and morphological assays, which confirmed apoptotic cell death (ca. 80-90%) predominantly through the involvement of reactive oxygen species. Interestingly, we observed that 2 mg kgDSPE-1 induced enhanced apoptosis and efficient inhibition of the growth of breast tumor xenografts in NOD/SCID mice models. Herein, we demonstrated the application of aza-BODIPY nanomicelles in photodynamic therapy for the first time, and our results revealed that the DSPE-BODIPY nanomicelles enhanced the cellular uptake as well as the photodynamic activity, thereby demonstrating the use of these nanomicelles as efficient sensitizers in biological applications.