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.