posted on 2021-04-12, 15:38authored byVanitha Ramu, Paramita Kundu, Paturu Kondaiah, Akhil R. Chakravarty
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.