Rational Design of an AIE-Active BODIPY-Quinolone-Imidazole Conjugate for Effective Photodynamic Therapy of Breast Cancer Cells.

Photodynamic therapy (PDT) has found itself as one of the leading cancer therapeutic modalities, owing to its minimally invasive nature. The outcomes of PDT can be improved with the development of efficient photosensitizers (PSs). The present work describes the development of three photosensitizers (C1, C2, and C3) by reigning in the photophysical attributes of heavy atom-free boron dipyrromethenes (BODIPYs) based on an imidazole-quinolone-BODIPY conjugate connected through 1,2,3-triazole linkers. The intricate molecular construct of these PSs has endowed two PSs (C2, C3) with an aggregation-induced emission (AIE) attribute and very high singlet generation quantum yields (87%, C2; 89%, C3). The generation of triplet excited states and relative spin-orbit coupling has been assessed via DFT and time-dependent density function theory (TD-DFT) studies. Through an in vitro cytotoxicity assay, C2 reveals a higher cytotoxic potential than its corresponding ligand L2 against T-47D breast cancer cells while sparing normal cells (HEK-293). Further, the cellular uptake study reveals that C2 preferentially localizes in the cytosol of T-47D breast cancer cells. DCFH-DA (dichloro-dihydro-fluorescein diacetate) staining reveals the reactive oxygen species (ROS) generation potency of C2, leading to apoptosis by disrupting the cellular functions in the G2/M phase of the cell cycle. Additionally, the in vitro scratch assay suggests the antiproliferative activity of C2 with reduced metastatic potential against T-47D cells. Also, C2 has the potential to alter key proteins involved in apoptosis and cell cycle progression, which was detected through the Western blot technique.