title: Albumin nanoparticles for glutathione-responsive release of cisplatin: New opportunities for medulloblastoma.
abstract: Redox-responsive nanoparticles were synthesized by desolvation of bovine serum albumin followed by disulfide-bond crosslinking with N, N'-Bis (acryloyl) cystamine. Dynamic light scattering and transmission electron microscopy studies revealed spherical nanoparticles (mean diameter: 83nm, polydispersity index: 0.3) that were glutathione-responsive. Confocal microscopy revealed rapid, efficient internalization of the nanoparticles by Daoy medulloblastoma cells and healthy controls (HaCaT keratinocytes). Cisplatin-loaded nanoparticles with drug:carrier ratios of 5%, 10%, and 20% were tested in both cell lines. The formulation with the highest drug:carrier ratio reduced Daoy and HaCaT cell viability with IC50values of 6.19 and 11.17μgmL-1, respectively. The differential cytotoxicity reflects the cancer cells' higher glutathione content, which triggers more extensive disruption of the disulfide bond-mediated intra-particle cross-links, decreasing particle stability and increasing their cisplatin release. These findings support continuing efforts to improve the safety and efficacy of antineoplastic drug therapy for pediatric brain tumors using selective nanoparticle-based drug delivery systems.
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome 00161, Italy; Pasteur Institute Italy, Fondazione Cenci Bolognetti, Rome 00161, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Catanzaro
authors.affiliation: Department of Pharmacy Health and Nutritional Science, University of Calabria, Rende 87036, Italy. Electronic address: manuela.curcio@unical.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Curcio
authors.affiliation: Department of Pharmacy Health and Nutritional Science, University of Calabria, Rende 87036, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirillo
authors.affiliation: Department of Pharmacy Health and Nutritional Science, University of Calabria, Rende 87036, Italy.
authors.forename: Umile Gianfranco
authors.initials: UG
authors.lastname: Spizzirri
authors.affiliation: Department of Molecular Medicine, Sapienza University, Rome 00161, Italy.
authors.forename: Zein Mersini
authors.initials: ZM
authors.lastname: Besharat
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome 00161, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Abballe
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome 00161, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vacca
authors.affiliation: Department of Pharmacy Health and Nutritional Science, University of Calabria, Rende 87036, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Iemma
authors.affiliation: Department of Pharmacy Health and Nutritional Science, University of Calabria, Rende 87036, Italy.
authors.forename: Nevio
authors.initials: N
authors.lastname: Picci
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome 00161, Italy; Neuromed Institute, Pozzilli 86077, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002528:Cerebellar Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008527:Medulloblastoma / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012710:Serum Albumin, Bovine; D005978:Glutathione; D002945:Cisplatin
keywords: Albumin nanoparticles; Biocompatibility; Cisplatin; Glutathione; Medulloblastoma; Redox responsivity