Photoactivable ruthenium-based coordination polymer nanoparticles for light-induced chemotherapy

Open Access

Abstract

Green light photoactive Ru-based coordination polymer nanoparticles (CPNs), with chemical formula [[Ru(biqbpy)] (bis)](PF) (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 di-ameter) 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) ](PF) (Complex 2). After irradiation (520 nm, 39.3 J/cm), 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 O 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. ; his work was supported by grant RTI2018-098027-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. With the support from "Metalfármacos multifuncionales para el diagnóstico y la terapia" with grant RED2018-102471-T funded by MCIN/AEI/10.13039/501100011033. The ICN2 is funded by the CERCA programme/Generalitat de Catalunya. The ICN2 is supported by the Severo Ochoa Centres of Excellence programme, grant SEV-2017-0706 funded by MCIN/AEI/10.13039/501100011033. J.D. Zhang thanks the BIST PhD Fellowship Programme (This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754558). NWO is kindly acknowledged for financial support to SB via a VICI grant. COST is kindly acknowledged for stimulating scientific discussion and financial support via the Cost Action CA 17140 "Cancer nanomedicine from the bench to the bedside".