Photocytotoxic cancer cell-targeting platinum(ii) complexes of glucose-appended curcumin and biotinylated 1,10-phenanthroline†
Mixed-ligand platinum(II) complexes, [Pt(phen)(pacac)](NO3) (1), [Pt(phen)(cur)](NO3) (2), [Pt(bt-phen)(cur)](NO3) (3) and [Pt(phen)(scur)](NO3) (4), where phen is 1,10-phenanthroline, bt-phen is 5-biotin-1,10-phenanthroline, pacac is 1,3-diphenyl-1,3-propanedioate anion, Hcur is curcumin and Hscur is diglucosylcurcumin, were prepared, characterized and their anticancer activity studied. Complexes 2–4 showed absorption bands within 410–430 nm (ε, 2.1 × 104 to 2.8 × 104 M−1 cm−1) in 10% DMSO–DPBS (Dulbecco's phosphate-buffered saline) and emission bands near 530 nm (λex = 410–430 nm) with a fluorescence quantum yield (ΦF) value of ∼0.02. The curcumin complexes showed stability over a study period of 48 h. The photocytotoxicity was studied using human cervical HeLa, human liver HepG2, human breast cancer MDA-MB 231 and human lung adenocarcinoma A549 cancer cells along with human immortalized lung epithelial HPL1D as normal cells. Complexes 2–4 showed apoptotic photo-induced cell death in light of wavelength 400–700 nm (IC50, half maximal inhibitory concentration: 6–28 μM) by reactive oxygen species (ROS), while remaining inactive in the dark (IC50: 43–95 μM). The selectivity of the complexes 3 and 4 was enhanced significantly towards the cancer cells than towards the normal cells, thus making them targeted photochemotherapeutic agents. The ROS formation and mode of cell death were studied from 2′,7′-dichlorofluorescein diacetate (DCFDA) and annexin-V/FITC (fluorescein isothiocyanate)-PI assays, respectively. Preferential nuclear and mitochondrial localization was evidenced from inductively coupled plasma mass spectrometry (ICP-MS) studies.