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

Abstract

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.

Near-infrared BODIPY photosensitizers for two-photon excited singlet oxygen generation and tumor cell photodynamic therapy

“…21–25 A similar organelle targeting strategy not only enhances the accumulation of photosensitizers in tumor cells, but also reduces the damage to normal cells, improving the efficacy and safety of photodynamic therapy. 26–28 In addition, photosensitizers with two-photon absorption properties can generate reactive oxygen species under NIR light excitation, thus realizing two-photon photodynamic therapy for tumor cells. 29–31 The wavelength of the light source used for two-photon excitation is longer and penetrates deeper into biological tissues.…”