Albumin nanoparticles for glutathione-responsive release of cisplatin: New opportunities for medulloblastoma

Giuseppina Catanzaro, Manuela Curcio, Giuseppe Cirillo, Umile Gianfranco Spizzirri, Zein Mersini Besharat, Luana Abballe, Alessandra Vacca, Francesca Iemma, Nevio Picci, Elisabetta Ferretti

Research output: Contribution to journalArticlepeer-review

Abstract

Redox-responsive nanoparticles were synthesized by desolvation of bovine serum albumin followed by disulfide-bond crosslinking with N, Nʹ-Bis (acryloyl) cystamine. Dynamic light scattering and transmission electron microscopy studies revealed spherical nanoparticles (mean diameter: 83 nm, 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 11.17 μg mL−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.

Original languageEnglish
Pages (from-to)168-174
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume517
Issue number1-2
DOIs
Publication statusPublished - Jan 30 2017

Keywords

  • Albumin nanoparticles
  • Biocompatibility
  • Cisplatin
  • Glutathione
  • Medulloblastoma
  • Redox responsivity

ASJC Scopus subject areas

  • Pharmaceutical Science

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