Ruthenium(II) Conjugates of Boron-Dipyrromethene and Biotin for Targeted Photodynamic Therapy in Red Light

Abstract

The ruthenium­(II) complexes [RuCl­(L1)­(L3)]Cl (1), [RuCl­(L1)­(L4)]­Cl (2), [RuCl­(L2)­(L4)]Cl (3), [RuCl­(L1)­(L5)]Cl (4), and [RuCl­(L2)­(L5)]Cl (5) of NNN-donor dipicolylamine (dpa) bases (L4, L5) having BODIPY (boron-dipyrromethene) moieties, NN-donor phenanthroline derivatives (L1, L2), and benzyldipicolylamine (bzdpa, L3) were prepared and characterized by spectroscopic techniques and their cellular localization/uptake and photocytotoxicity studied. Complex 1, as its PF6 salt (1a), has been structurally characterized with help of a single-crystal X-ray diffraction technique. It has a RuN5Cl core with the Cl bonded trans to the amine nitrogen atom of bzdpa. The complexes showed intense absorption spectral bands near 500 nm (ε ≈ 58000 M–1 cm–1) in 2 and 3 and 654 nm (ε ≈ 80000 M–1 cm–1) in 4 and 5 in 1/1 DMSO/DPBS (v/v). Complex 5 having biotin and PEGylated-disteryl BODIPY gave a singlet oxygen quantum yield (ΦΔ) of ∼0.65 in DMSO. Complex 5 exhibited remarkable PDT (photodynamic therapy) activity (IC50 ≈ 0.02 μM) with a photocytotoxicity index (PI) value of >5000 in red light of 600–720 nm in A549 cancer cells. The biotin-conjugated complexes showed better photocytotoxicity in comparison to nonbiotinylated analogues in A549 cells. The complexes displayed less toxicity in HPL1D normal cells in comparison to A549 cancer cells. The emissive BODIPY complexes 3 and 5 (ΦF ≈ 0.07 in DMSO) showed significant mitochondrial localization.

Strategies to promote permeation and vectorization, and reduce cytotoxicity of metal complex luminophores for bioimaging and intracellular sensing

“…Biotinylation of anthracene modified Ru(II) complexes was also shown to be effective at promoting uptake in cancerous cell lines. 88 Fig. 11 Zinc and osmium dyes reported for use with super-resolution microscopy.…”

“…Biotinylation of anthracene modified Ru( ii ) complexes was also shown to be effective at promoting uptake in cancerous cell lines. 88 …”

Photodynamic Therapy of Inorganic Complexes for the Treatment of Cancer†

“…In the visible light, the complexes had IC 50 values of ∼2.0 and 0.98 μ m in A549 cells. The photocytotoxicity of the complexes was reduced by ∼4‐fold in the HPL1Dcell line (103).…”

Emerging Molecular Receptors for the Specific-Target Delivery of Ruthenium and Gold Complexes into Cancer Cells

“…An extensive number of inorganic and organometallic gold and ruthenium complexes have been conjugated to several different biomolecules for targeted anticancer purposes. These include systems targeting the amino acid transporters [ 102 , 106 , 107 , 108 , 109 ], peptide transporters [ 110 , 111 ], glucose transporters [ 69 , 112 , 113 ], and vitamin transporters [ 77 , 114 , 115 , 116 , 117 , 118 ]. As our review mainly focuses on the emerging receptors for the target delivery of ruthenium and gold complexes into cancer cells, for which the use of biomolecules as delivering carriers is well-known and is out of our scope, we will not discuss them in further detail.…”