Abstract
Green light photoactive Ru-based coordination polymer nanoparticles (CPNs), with chemical formula [[Ru(biqbpy)]1.5(bis)](PF6)3 (biqbpy = 6,6′-bis[N-(isoquinolyl)-1-amino]-2,2′-bipyridine; bis = bis(imidazol-1-yl)-hexane), were obtained through polymerization of the trans-[Ru(biqbpy)(dmso)Cl]Cl complex (Complex 1) and bis bridging ligands. The as-synthesized CPNs (50 ± 12 nm diameter) showed high colloidal and chemical stability in physiological solutions. The axial bis(imidazole) ligands coordinated to the ruthenium center were photosubstituted by water upon light irradiation in aqueous medium to generate the aqueous substituted and active ruthenium complexes. The UV-Vis spectral variations observed for the suspension upon irradiation corroborated the photoactivation of the CPNs, while High Performance Liquid Chromatography (HPLC) of irradiated particles in physiological media allowed for the first time precisely quantifying the amount of photoreleased complex from the polymeric material. In vitro studies with A431 and A549 cancer cell lines revealed an 11-fold increased uptake for the nanoparticles compared to the monomeric complex [Ru(biqbpy)(N-methylimidazole)2](PF6)2 (Complex 2). After irradiation (520 nm, 39.3 J/cm2), the CPNs yielded up to a two-fold increase in cytotoxicity compared to the same CPNs kept in the dark, indicating a selective effect by light irradiation. Meanwhile, the absence of 1O2 production from both nanostructured and monomeric prodrugs concluded that light-induced cell death is not caused by a photodynamic effect but rather by photoactivated chemotherapy.
Highlights
Ruthenium-based drugs have raised interest over the last years as an alternative to Pt drugs for oncotherapy, with an increasing number of them entering clinical trials, such as NAMI-A, KP 1019, KP 1339, or TLD–1433 [1,2,3,4,5,6,7]
Afterwards, the solution was cooled down to room temperature, and a saturated KPF6 solution was added to the mixture, resulting in a brown precipitate
Precise control of the reaction conditions led to the reproducible synthesis of narrow size distribution (50 ± 12 nm) coordination polymer nanoparticles (CPNs) with
Summary
Ruthenium-based drugs have raised interest over the last years as an alternative to Pt drugs for oncotherapy, with an increasing number of them entering clinical trials, such as NAMI-A, KP 1019, KP 1339, or TLD–1433 [1,2,3,4,5,6,7]. Relevant has been the development of ruthenium prodrug molecular complexes bearing photolabile ligands for photoactivated chemotherapy (PACT) applications [8,9,10,11,12] These complexes generally exhibit low toxicity in the dark but become toxic once activated by visible light irradiation. PACT is an oxygen-independent activation mechanism that works even under hypoxic conditions This feature makes it potentially more versatile than type II photodynamic therapy (PDT), which requires the presence of a significant amount of dioxygen to generate enough reactive singlet oxygen species to induce cytotoxicity [10,11,14,18,19,20,21,22,23,24]
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