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

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

来源：International Journal of Pharmaceutics, 2017, 517(1-2): 168-174.

DOI：10.1016/j.ijpharm.2016.12.017

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

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: 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 IC50 values of 6.19 and 11.17 mu g 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.

• 出版日期2017-1-30