Functionalized nonporous silica nanoparticles as carriers for Pt(iv) anticancer prodrugsElectronic supplementary information (ESI) available: TEM characterization of SNPs, properties of SNPs d and e, 29Si{1H} CPMAS NMR spectrum of d, % Pt loading with respect to reaction time and Pt/NH2 group ratio. See DOI: 10.1039/c6dt03133a

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. Conjugate Pt( iv )-silica nanoparticles exhibited better antiproliferative activity than cisplatin and Pt( iv ) precursors, due to their more efficient cellular uptake.