{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Guegain E"],"funding":["Agence Nationale de la Recherche"],"pagination":["8291-8306"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6240899"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(43)"],"pubmed_abstract":["Degradable polymer prodrugs based on gemcitabine (Gem) as an anticancer drug were synthesized by 'drug-initiated' nitroxide-mediated radical ring-opening copolymerization (NMrROP) of methacrylic esters and 2-methylene-4-phenyl-1,3-dioxolane (MPDL). Different structural parameters were varied to determine the best biological performances: the nature of the monomer [<i>i.e.</i>, oligo(ethylene glycol) methacrylate (OEGMA) or methyl methacrylate (MMA)], the nature of the Gem-polymer linker (<i>i.e.</i>, amide or amide and diglycolate) and the MPDL content in the copolymer. Depending on the nature of the methacrylate monomer, two small libraries of water-soluble copolymer prodrugs and nanoparticles were obtained (<i>M</i> <sub>n</sub> ∼10 000 g mol<sup>-1</sup>, <i>Đ</i> = 1.1-1.5), which exhibited tunable hydrolytic degradation under accelerated conditions governed by the MPDL content. Drug-release profiles in human serum and <i>in vitro</i> anticancer activity on different cell lines enabled preliminary structure-activity relationships to be established. The cytotoxicity was independently governed by: (i) the MPDL content - the lower the MPDL content, the greater the cytotoxicity; (ii) the nature of the linker - the presence of a labile diglycolate linker enabled a greater Gem release compared to a simple amide bond and (iii) the hydrophilicity of the methacrylate monomer-OEGMA enabled a greater anticancer activity to be obtained compared to MMA-based polymer prodrugs. Remarkably, the optimal structural parameters enabled reaching the cytotoxic activity of the parent (free) drug."],"journal":["Chemical science"],"pubmed_title":["Degradable polymer prodrugs with adjustable activity from drug-initiated radical ring-opening copolymerization."],"pmcid":["PMC6240899"],"funding_grant_id":["ANR-15-CE08-0019","ANR-11-JS08-0005"],"pubmed_authors":["Deguettes Q","Nicolas J","Guegain E","Tran J"],"additional_accession":[]},"is_claimable":false,"name":"Degradable polymer prodrugs with adjustable activity from drug-initiated radical ring-opening copolymerization.","description":"Degradable polymer prodrugs based on gemcitabine (Gem) as an anticancer drug were synthesized by 'drug-initiated' nitroxide-mediated radical ring-opening copolymerization (NMrROP) of methacrylic esters and 2-methylene-4-phenyl-1,3-dioxolane (MPDL). Different structural parameters were varied to determine the best biological performances: the nature of the monomer [<i>i.e.</i>, oligo(ethylene glycol) methacrylate (OEGMA) or methyl methacrylate (MMA)], the nature of the Gem-polymer linker (<i>i.e.</i>, amide or amide and diglycolate) and the MPDL content in the copolymer. Depending on the nature of the methacrylate monomer, two small libraries of water-soluble copolymer prodrugs and nanoparticles were obtained (<i>M</i> <sub>n</sub> ∼10 000 g mol<sup>-1</sup>, <i>Đ</i> = 1.1-1.5), which exhibited tunable hydrolytic degradation under accelerated conditions governed by the MPDL content. Drug-release profiles in human serum and <i>in vitro</i> anticancer activity on different cell lines enabled preliminary structure-activity relationships to be established. The cytotoxicity was independently governed by: (i) the MPDL content - the lower the MPDL content, the greater the cytotoxicity; (ii) the nature of the linker - the presence of a labile diglycolate linker enabled a greater Gem release compared to a simple amide bond and (iii) the hydrophilicity of the methacrylate monomer-OEGMA enabled a greater anticancer activity to be obtained compared to MMA-based polymer prodrugs. Remarkably, the optimal structural parameters enabled reaching the cytotoxic activity of the parent (free) drug.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Nov","modification":"2025-04-04T08:41:51.313Z","creation":"2019-10-30T08:14:15Z"},"accession":"S-EPMC6240899","cross_references":{"pubmed":["30542578"],"doi":["10.1039/c8sc02256a"]}}