d9e73f2dd6ffbcdf8ae51a26afd3fa27 pmc_34835853.pdf fe03ac6ac00521e98e40744d09cfc6382f0b0987 pmc_34835853.pdf 634818e4dbc802f324397433fda42ba17d3416f9e1261fd58259242519eb61b9 pmc_34835853.pdf Title: Photoactivable Ruthenium-Based Coordination Polymer Nanoparticles for Light-Induced Chemotherapy Subject: 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. Keywords: coordination polymer nanoparticles; nanoparticles; photoactivated chemotherapy; prodrug; drug delivery; ruthenium-based drug Author: Junda Zhang, Vadde Ramu, Xue-Quan Zhou, Carolina Frias, Daniel Ruiz-Molina, Sylvestre Bonnet, Claudio Roscini and Fernando Novio Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Nov 24 11:25:02 2021 CET ModDate: Wed Nov 24 11:27:48 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1921857 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CRZVTG+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 RTFWOX+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 AIYADA+URWPalladioL-Roma Type 1 Custom yes yes no 19 0 PAXHIV+CMSY10 Type 1 Builtin yes yes no 23 0 NPLVPL+TimesNewRomanPS-BoldItalicMT Type 1C 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Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Reagents and Instrumentation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Synthesis and Characterization of the Photoactive Materials Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: Synthesis of Complex 2 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Synthesis of Coordination Polymer Nanoparticles RuBIS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: HPLC Methodology for RuBIS CPNs Releasing Quantification Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Quantitative 1H NMR and 19F NMR for Component Analysis of RuBIS CPNs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: In Vitro Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Cell Culturing Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Cell-Irradiation Setup Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Cytotoxicity Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Cellular Uptake Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Endocytosis Inhibition Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: ICP-MS Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Singlet Oxygen (1O2) Production Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Children: Item: Title: Synthesis and Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Photoreactivity of RuBIS CPNs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Children: Item: Title: Monitorization by UV-Vis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: HPLC Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Cellular Uptake Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: (Photo)cytotoxicity Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Singlet Oxygen Production Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Info: Title: Photoactivable Ruthenium-Based Coordination Polymer Nanoparticles for Light-Induced Chemotherapy Author: Junda Zhang, Vadde Ramu, Xue-Quan Zhou, Carolina Frias, Daniel Ruiz-Molina, Sylvestre Bonnet, Claudio Roscini and Fernando Novio Subject: 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. 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