Glucose-Appended Platinum(II)-BODIPY Conjugates for Targeted Photodynamic Therapy in Red Light

Abstract

Platinum(II) complexes [Pt(L1)(R-BODIPY)]Cl (1) and [Pt(L2)(R-BODIPY)]Cl (2), where R-BODIPY is 8-(4-ethynylphenyl)-distyryl-4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3, L1 is 4′-phenyl-2,2′:6′,2″-terpyridine, and L2 is (2,2′:6′,2″-terpyridin-4′-oxy)ethyl-β-d-glucopyranoside, were synthesized and characterized, and their photocytotoxicity was studied. The phenylacetylide complex [Pt(L1)(C≡CPh)]Cl (3) was prepared and used as a control. Complexes 1 and 2 showed near-IR absorption bands at 713 nm (ε = 3.47 × 104 M–1 cm–1) and 715 nm (3.2 × 104 M–1 cm–1) in 10% dimethyl sulfoxide (DMSO)–Dulbecco’s Modified Eagle’s Medium (DMEM) (pH 7.2). The BODIPY complexes are emissive in 10% DMSO–DMEM at pH 7.2 with λem (λex, Φf) = 822 nm (710 nm, 0.022) for complex 1 and λem (λex, Φf) = 825 nm (710 nm, 0.026) for complex 2. They generated singlet oxygen (1O2) in red light as evidenced from 1,3-diphenylisobenzofuran (DPBF) titration experiments. The singlet oxygen quantum yield (ΦΔ) values for 1 and 2 were ∼0.6 signifying their photosensitizing ability. They were remarkably photodynamic therapy (PDT) active in red light showing significant red light-induced cytotoxicity in cervical HeLa, lung cancer A549, and breast cancer MCF-7 cells (IC50: 2.3–24.7 μM in light) with negligible dark toxicity (IC50 > 100 μM). A significant enhancement in cellular uptake was observed for 2 having glucose-appended terpyridine ligand compared to 1. The confocal microscopy showed significant mitochondrial localization of the complexes as evidenced from the JC-1 assay. The complexes released the photoactive R-BODIPY ligand upon red light-irradiation as evidenced from the mass and 1H NMR spectral studies. Complex 2 is remarkable in satisfying the essential requirements of targeted PDT in red light.