NIR ditriphenylamine Indole-BODIPY photosensitizer: synthesis, photodynamic therapy in A549 cells and two-photon fluorescence imaging in zebrafish.

Abstract

In this study, the ditriphenylamine Indole-BODIPY photosensitizer T₂BDP-lyso was synthesized for near-infrared photodynamic therapy and two-photon fluorescence imaging. The photosensitizer T₂BDP-lyso exhibits absorption above 700 nm and emission above 800 nm, respectively. Theoretical calculations show the energy gap from the excited state S₁ to the excited state T₂ is 0.14 eV, which indicated that the photosensitizer T₂BDP-lyso could reach the triplet state by intersystem crossing from the singlet state. Under NIR light, the singlet oxygen yield of photosensitizer T₂BDP-lyso was calculated to be 0.64 in CH₂Cl₂. The photosensitizer T₂BDP-lyso can effectively produce reactive oxygen species in A549 cells and zebrafish under 660 nm light for 5 min. The photosensitizer T₂BDP-lyso exhibited lower dark toxicity and higher phototoxicity (IC₅₀ = 1.49 μM), as well as lysosomal targeting ability (Pearson coefficient = 0.89). In the AO/EB double staining assay simulating photodynamic therapy at the cellular level, 3 μM of T₂BDP-lyso light for 10 min was effective in killing cancer cells. Moreover, the photosensitizer T₂BDP-lyso has a large two-photon absorption cross section at 1050 nm, which was calculated to be 138.7 GM in THF by Z-scan method, and two-photon fluorescence imaging was performed in zebrafish. The above results indicate the potential application of the photosensitizer T₂BDP-lyso in near-infrared photodynamic therapy and two-photon fluorescence imaging.