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.
Albumin nanoparticles for glutathione-responsive release of cisplatin: new opportunities for medulloblastoma treatment
CATANZARO, GIUSEPPINA;
2017-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
