Mitochondria‐Targeting Boron Dipyrromethene Based Photosensitizers for Enhanced Photodynamic Therapy: Synthesis, Optical Properties, and in vitro Biological Activity

Abstract

Increasing Investigations show that photosensitizers (PSs) which target mitochondria are useful for enhancing photodynamic therapy (PDT) efficacy. Herein, we carefully designed and synthesized four triphenylphosphonium (TPP)-modified boron dipyrromethene (BDP)-based PSs through Cu(I)-assisted "3 + 2" cycloaddition reaction. All of them exhibit intense red light absorption with maxima between 659 and 663 nm, considerable fluorescence emission with quantum yields of 0.16-0.23, high singlet oxygen generation efficiency ranging from 0.22 to 0.34, excellent mitochondria-targeting ability, and good biocompatibility. Upon illumination, they induce significant cancer cell death through a mitochondria-related apoptosis pathway. The IC 50 values of these BDP dyes against MCF-7 cells were determined to be as low as 0.046-0.113 μM under rather low dosage of light irradiation (1.5 J • cm À 2 ).

Lysosomes Targeting pH Activable Imaging‐Guided Photodynamic Agents

“…Indeed, compared to the two latter producing respectively 1 O 2 in 87 % and 64 % quantum yields (see SI), the values are here lower. However, they are comparable to those reported for some bis‐iodo BODIPY derivatives with (or without) quenching functional groups, considering the different experimental conditions [40,41,51,75–77] . As expected, no 1 O 2 production was observed in the absence of protonation of the amino groups (see SI).…”

Mitochondria-targeted BODIPY dyes for small molecule recognition, bio-imaging and photodynamic therapy

“…As a result, a series of PEG-modified PDT agents 61a-62d were produced to effectively improve the uptake capacity and prevent intracellular dye aggregation. 170,171 In addition, Gunbas et al developed a potent mitochondria-targeted PS, 63, leveraging the double heavy atom effect of selenium and iodine. 172 The probe exhibits highly selective photocytotoxicity against cancer cells even under hypoxic conditions, making it an excellent candidate for the development of next-generation PDT drugs to treat hypoxic solid tumors.…”