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

Abstract

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 λem value of 720 nm in 10% DMSO–DMEM (pH 7.2) upon excitation (λex) at 615 nm with a large Stokes shift. The fluorescence quantum yield (ΦF) 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.

BODIPY Conjugates as Functional Compounds for Medical Diagnostics and Treatment

“…A conjugate 12 based on monoaminostyryl-substituted BODIPY (Scheme 7) was presented by the authors of the article [12]. The conjugate is characterized by absorption bands at 617 nm (ε = 2.9 × 10 4 M −1 cm −1 ) in pH 7.2 10% DMSO/DMEM buffer (v/v).…”

“…This means that complex 12 interacts with DNA through groove binding and/or an intercalative mode. The authors' results of [12] showed that 12 is capable of singlet oxygen generation and exhibits a remarkable PDT effect along with a DNA binding interaction with the possibility of inducing a chemotherapeutic effect.…”

Fluorescence Microscopy—An Outline of Hardware, Biological Handling, and Fluorophore Considerations

“…Organic fluorophores have also found use as effective therapeutic agents harnessing their absorptive properties to give rise to photo-dynamic therapy. For example, a cisplatin-BODIPY conjugate was recently reported which was found to initiate ROS upon irradiation with near-IR light to invoke a cytotoxic response to A549 and HeLa cancer cells [ 286 ]. This conjugate was found to localise within the mitochondria of cells, which is the major cite of ROS production.…”

BODIPY–dipicolylamine complexes of platinum(ii): X-ray structure, cellular imaging and organelle-specific near-IR light type-II PDT

“…27,28 In addition, the red and green light-active BODIPY-based platinum( ii ) complexes with different molecular designs reported earlier by us had catecholate or other O,O-donor ligands lacking similarity to the present complexes. 29–32 The review article of Guo and co-workers highlights the recent advancements in monofunctional platinum( ii ) chemistry. 33…”