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EnglishPlatinum 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.
| Titolo: | Multifunctional Platinum@BSA-Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation | |
| Autori Riconosciuti: | ||
| Autori: | De Luca, Elisa; Pedone, Deborah; Moglianetti, Mauro; Pulcini, Daniele; Perrelli, Andrea; Retta, Saverio Francesco; Pompa, Pier Paolo | |
| Data di pubblicazione: | 2018 | |
| Abstract: | 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. | |
| Volume: | 3 | |
| Fascicolo: | 11 | |
| Pagina iniziale: | 15389 | |
| Pagina finale: | 15398 | |
| Digital Object Identifier (DOI): | 10.1021/acsomega.8b01653 | |
| URL: | https://pubs.acs.org/doi/abs/10.1021/acsomega.8b01653 https://pubs.acs.org/doi/pdf/10.1021/acsomega.8b01653 | |
| Parole Chiave: | Cerebral Cavernous Malformation (CCM), Oxidative stress-related diseases, Platinum nanoparticles (PtNPs), Multifunctional nanocarriers, Redox signaling, Autophagy | |
| Rivista: | ACS OMEGA | |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
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| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 2018 ACS Omega - Multifunctional Platinum@BSA–Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation.pdf | Articolo principale | PDF EDITORIALE | Open Access Visualizza/Apri |
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