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Multifunctional Platinum@BSA–Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation

[Image: see text] Platinum nanoparticles (PtNPs) are antioxidant enzyme-mimetic nanomaterials with significant potential for the treatment of complex diseases related to oxidative stress. Among such diseases, Cerebral Cavernous Malformation (CCM) is a major cerebrovascular disorder of genetic origin...

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Detalles Bibliográficos
Autores principales: De Luca, Elisa, Pedone, Deborah, Moglianetti, Mauro, Pulcini, Daniele, Perrelli, Andrea, Retta, Saverio Francesco, Pompa, Pier Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288776/
https://www.ncbi.nlm.nih.gov/pubmed/30556006
http://dx.doi.org/10.1021/acsomega.8b01653
Descripción
Sumario:[Image: see text] Platinum nanoparticles (PtNPs) are antioxidant enzyme-mimetic nanomaterials with significant potential for the treatment of complex diseases related to oxidative stress. Among such diseases, Cerebral Cavernous Malformation (CCM) is a major cerebrovascular disorder of genetic origin, which affects at least 0.5% of the general population. Accumulated evidence indicates that loss-of-function mutations of the three known CCM genes predispose endothelial cells to oxidative stress-mediated dysfunctions by affecting distinct redox-sensitive signaling pathways and mechanisms, including pro-oxidant and antioxidant pathways and autophagy. A multitargeted combinatorial therapy might thereby represent a promising strategy for the effective treatment of this disease. Herein, we developed a multifunctional nanocarrier by combining the radical scavenging activity of PtNPs with the autophagy-stimulating activity of rapamycin (Rapa). Our results show that the combinatorial targeting of redox signaling and autophagy dysfunctions is effective in rescuing major molecular and cellular hallmarks of CCM disease, suggesting its potential for the treatment of this and other oxidative stress-related diseases.