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

Redox-responsive nanoparticles were synthesized by desolvation of bovine serum albumin followedby disulfide-bond crosslinking with N, Nʹ-Bis (acryloyl) cystamine. Dynamic light scattering andtransmission 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%, and20% were tested in both cell lines. The formulation with the highest drug:carrier ratio reduced Daoyand HaCaT cell viability with IC50 values of 6.19 and 11.17 μg mL-1, respectively. The differentialcytotoxicity reflects the cancer cells’ higher glutathione content, which triggers more extensivedisruption of the disulfide bond-mediated intra-particle cross-links, decreasing particle stability andincreasing their cisplatin release. These findings support continuing efforts to improve the safetyand efficacy of antineoplastic drug therapy for pediatric brain tumors using selective nanoparticlebaseddrug delivery systems.