title: Functionalized nonporous silica nanoparticles as carriers for Pt(iv) anticancer prodrugs.
abstract: Nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups were proposed as potential delivery systems for Pt(iv) antitumor prodrugs. Spherical SNPs containing two different external arms, i.e. 3-aminopropyl and N-(6-aminohexyl)aminomethylene, of around 125 nm hydrodynamic diameter were loaded with two different cisplatin-based Pt(iv) complexes, namely (OC-6-44)-diamminedichloridoethoxidosuccinatoplatinum(iv) and (OC-6-44)-diamminedichloridoacetylamidosuccinatoplatinum(iv), through the formation of amide bonds between the pendant amino groups on SNPs and the free carboxylic group of the complexes. In the presence of the N-(6-aminohexyl)aminomethylene arm, the Pt(iv)-SNP conjugates showed a negligible (unwanted) Pt release by hydrolysis, whereas in the presence of ascorbic acid the reduction of Pt(iv) → Pt(ii) caused the substantial release of the active metabolite cisplatin. Conjugate Pt(iv)-SNP exhibited better antiproliferative activity on the Pt-sensitive A2780 human ovarian cancer cell line than the parent cisplatin and their free Pt(iv) precursors, due to their more efficient cellular uptake, likely by endocytosis.
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy. domenico.osella@uniupo.it.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-4732-7508
authors.initials: M
authors.lastname: Ravera
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy. domenico.osella@uniupo.it.
authors.forename: E
authors.identifier: http://orcid.org/0000-0002-1181-1955
authors.initials: E
authors.lastname: Gabano
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy. domenico.osella@uniupo.it.
authors.forename: I
authors.identifier: http://orcid.org/0000-0003-2174-508X
authors.initials: I
authors.lastname: Zanellato
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy. domenico.osella@uniupo.it.
authors.forename: E
authors.initials: E
authors.lastname: Perin
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy. domenico.osella@uniupo.it.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-0279-6180
authors.initials: A
authors.lastname: Arrais
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy. domenico.osella@uniupo.it.
authors.forename: D
authors.initials: D
authors.lastname: Osella
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004705:Endocytosis; D005260:Female; D006801:Humans; D006868:Hydrolysis; D053758:Nanoparticles / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000628:therapy; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009944:Organoplatinum Compounds; D011355:Prodrugs; D012822:Silicon Dioxide; D001205:Ascorbic Acid; D002945:Cisplatin