Maloplatin-B, a Cisplatin-Based BODIPY-Tagged Mito-Specific “Chemo-PDT” Agent Active in Red Light

Maloplatin-B, a cisplatin-based complex, namely [Pt­(A-BOD)­(NH₃)₂]­(NO₃) (Pt-A-BOD) with a pendant boron-dipyrromethene (BODIPY) moiety, where HA-BOD is a methyl malonyl chloride derived monostyryl BODIPY ligand, was designed and developed as near-IR light (600–720 nm) organelle-targeting photodynamic therapy agent. The complex [Pt­(acac)­(NH₃)₂]­(NO₃) (Pt-Ac) was used as a control. Pt-A-BOD displayed an absorption band at 616 nm (ε = 2.9 × 10⁴ M^–1 cm^–1) in 10% dimethyl sulfoxide/Dulbecco’s Modified Eagle’s Medium (DMSO/DMEM, pH 7.2). This complex displayed a broad emission band within 650–850 nm with a λ_em value of 720 nm in 10% DMSO–DMEM (pH 7.2) upon excitation (λ_ex) at 615 nm with a large Stokes shift. The fluorescence quantum yield (Φ_F) value for Pt-A-BOD is 0.032 and for the ligand HA-BOD is 0.24. The BODIPY complex and ligand showed the formation of singlet oxygen as the ROS (reactive oxygen species) on irradiation with near-IR red light of 660 nm, as evidenced from a 1,3-diphenylisobenzofuran (DPBF) assay. The complex displayed remarkable apoptotic NIR light-induced PDT activity with half-maximum inhibitory concentration values (IC₅₀) of 1.6–2.4 μM in A549 lung and HeLa cervical cancer cells, while it was less active in the dark. The cellular ROS generation by the complex in red light was ascertained by a DCFDA (2′,7′-dichlorofluorescein diacetate) assay. Cellular imaging showed its localization primarily in the mitochondria of A549 cancer cells. The JC1 and Annexin-V FITC/PI assays carried out for A549 cancer cells treated with the BODIPY complex showed the alteration of mitochondrial membrane potential and apoptotic cell death on near-IR red light (600–720 nm) irradiation, respectively.