A novel heavy-atom-free lysosome-targeted BODIPY as triplet photosensitizer based on SOCT-ISC mechanism for photodynamic therapy

Abstract

As important organelles in biological cells, lysosomes are closely associated with cell signaling, necrosis and apoptosis. Herein, we report a novel lysosome-targeted boron dipyrromethene (BODIPY) photosensitizer, Lyso-BDP, which has the advantage of lower side effects and higher phototoxicity for 4T1 cells in photodynamic therapy (PDT). Lyso-BDP possesses the lysosomal targeting treatment through the production of the singlet oxygen under the light excitation at 600 nm. We combine the anthracenyl group and BODIPY to form a D-A binary compound. The orthogonal configuration is confirmed by density functional theory (DFT) and time-dependent density functional theory (TDDFT). The molecular orbitals and the energies of the triplet state explain the spin-orbit charge transfer inter-system crossing (SOCT-ISC) mechanism. Due to SOCT-ISC mechanism, Lyso-BDP has the high singlet oxygen (1O2) quantum yield of 62% in DCM without heavy atoms. In this way, the dark toxicity of photosensitizer can be reduced. Meanwhile, the 1O2 ″afterglow” can be achieved to enhance the phototherapeutic effect because of the anthracene group. Compared to classical photosensitizers, Lyso-BDP shows the low half maximum inhibitory concentration (IC50) of 2.5 μM for 4T1 cells in vitro cytotoxicity assays. Therefore, this work provides a strategy to solve the problem of high cellular dark toxicity and no organelle targeting of classical photosensitizers.