Discovery of Subcellular-Targeted Aza-BODIPY Photosensitizers for Efficient Photodynamic Antitumor Therapy

In
this study, we linked classical organelle-targeting groups,
such as triphenylphosphonium, pentafluorobenzene, and morpholine,
to our previously reported potent monoiodo Aza-BODIPY photosensitizer
(BDP-15). They were conveniently prepared and retained
the advantages of Aza-BODIPY PS with intense NIR absorption, moderate
quantum yield, potent photosensitizing efficiency, and good stability.
The in vitro antitumor assessment indicated that
mitochondria-targeting and lysosome-targeting groups were more effective
than ER-targeting groups. Considering undesirable dark toxicity of
triphenylphosphonium-modified PSs, compound 6 containing
amide-linked morpholine possessed a favorable dark/phototoxicity ratio
(>6900 for tumor cells) and was localized in lysosomes with Pearson’s
coefficient of 0.91 to Lyso-Tracker Green DND-26. 6 exhibited
significantly increased intracellular ROS production and resulted
in early/late apoptosis and necrosis to disrupt tumor cells. Moreover, in vivo antitumor efficacy exploration suggested that even
under a slightly low dose of light (30 J/cm2) and single-time
photoirradiation, 6 retarded tumor growth dramatically
and displayed much better PDT activity over BDP-15 and Ce6.