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

Abstract

Platinum(II) complexes [Pt(L)(R-BODIPY)]Cl (1) and [Pt(L)(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, L is 4'-phenyl-2,2':6',2″-terpyridine, and L 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(L)(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 × 10 M cm) and 715 nm (3.2 × 10 M cm) 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 λ (λ, Φ) = 822 nm (710 nm, 0.022) for complex 1 and λ (λ, Φ) = 825 nm (710 nm, 0.026) for complex 2. They generated singlet oxygen (O) in red light as evidenced from 1,3-diphenylisobenzofuran (DPBF) titration experiments. The singlet oxygen quantum yield (Φ) 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 (IC: 2.3-24.7 μM in light) with negligible dark toxicity (IC > 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 H NMR spectral studies. Complex 2 is remarkable in satisfying the essential requirements of targeted PDT in red light.

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Lysosome Specific Platinum(II) Catecholates with Photoactive BODIPY for Imaging and Photodynamic Therapy in Near‐IR Light

“…The higher accumulation of drug molecules into target cancer cells in comparison to the non‐cancerous cells can be achieved by appending vitamins, folic acids, peptides, glucose etc. on the drug molecule such that the activity of the drug molecule is not hindered [5–7] . Scientists have now developed an alternative method to enhance the efficacy and specificity by crafting the drug molecules to localize inside a specific organelle [8–10] .…”

“…on the drug molecule such that the activity of the drug molecule is not hindered. [5][6][7] Scientists have now developed an alternative method to enhance the efficacy and specificity by crafting the drug molecules to localize inside a specific organelle. [8][9][10] Organelle targeted therapy is being widely investigated for killing various cancer cells through apoptosis.…”