Platinum nanoparticles (PtNPs) are antioxidant enzymemimetic nanomaterials with significant potential for the treatment ofcomplex diseases related to oxidative stress. Among such diseases,Cerebral Cavernous Malformation (CCM) is a major cerebrovasculardisorder of genetic origin, which affects at least 0.5% of the generalpopulation. Accumulated evidence indicates that loss-of-functionmutations of the three known CCM genes predispose endothelial cellsto oxidative stress-mediated dysfunctions by affecting distinct redoxsensitive signaling pathways and mechanisms, including pro-oxidant andantioxidant pathways and autophagy. A multitargeted combinatorialtherapy might thereby represent a promising strategy for the effectivetreatment of this disease. Herein, we developed a multifunctionalnanocarrier by combining the radical scavenging activity of PtNPs withthe autophagy-stimulating activity of rapamycin (Rapa). Our resultsshow that the combinatorial targeting of redox signaling and autophagy dysfunctions is effective in rescuing major molecular andcellular hallmarks of CCM disease, suggesting its potential for the treatment of this and other oxidative stress-related diseases.
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