Novel indole-BODIPY photosensitizers based on iodine promoted intersystem crossing enhancement for lysosome-targeted imaging and photodynamic therapy

Abstract

In this work, we report the new lysosome-targeting indole-BODIPY derivatives BDP-Lys, IBDP-Lys, and I₂BDP-Lys. BDP-Lys dye was designed for fluorescence imaging through introduction of an indole-containing morpholine moiety to a BODIPY core. Monoiodine and diiodine were incorporated into BDP-Lys dye to develop the photosensitizers IBDP-Lys and I₂BDP-Lys. The maximum absorption (λ_abs) for IBDP-Lys and I₂BDP-Lys displayed a redshift at approximately 11 nm and 27 nm, respectively, compared with the BDP-Lys dye (λ_abs = 504 nm). Similarly, the maximum emission also exhibited a redshift. The fluorescence quantum yield (Φ_F) of IBDP-Lys (Φ_F = 0.37%) and I₂BDP-Lys (Φ_F = 0.71%) was much lower than that of BDP-Lys dye (Φ_F = 7.48%). The singlet oxygen quantum yields were measured as 43.10% for IBDP-Lys and 71.00% for I₂BDP-Lys, which were higher than the iodine-free dye BDP-Lys. The theoretical calculation reasonably explains that iodine atoms promoted the intersystem crossing (ISC) process, and di-iodine further enhanced the ISC in indole-BODIPY dyes. Moreover, monoiodine photosensitizer IBDP-Lys was able to balance the generation of singlet oxygen and biocompatibility in cancer treatment. IBDP-Lys exhibited low dark toxicity (cell viability >90%), satisfactory biocompatibility, and precise lysosome targeting, with a Pearson coefficient of 0.93. The IBDP-Lys photosensitizer also was able to kill tumour cells. Considering the above results, the novel structure of indole-BODIPY photosensitizers could serve as a potential platform for lysosome-targeted imaging and photodynamic therapy.