Oxidative stress
is known to be the cause of several
neurovascular
diseases, including neurodegenerative disorders, since the increase
of reactive oxygen species (ROS) levels can lead to cellular damage,
blood–brain barrier leaking, and inflammatory pathways. Herein,
we demonstrate the therapeutic potential of 5 nm platinum nanoparticles
(PtNPs) to effectively scavenge ROS in different cellular models of
the neurovascular unit. We investigated the mechanism underlying the
PtNP biological activities, analyzing the influence of the evolving
biological environment during particle trafficking and disclosing
a key role of the protein corona, which elicited an effective switch-off
of the PtNP catalytic properties, promoting their selectivein situactivity. Upon cellular internalization, the lysosomal
environment switches on and boosts the enzyme-like activity of the
PtNPs, acting as an intracellular “catalytic microreactor”
exerting strong antioxidant functionalities. Significant ROS scavenging
was observed in the neurovascular cellular models, with an interesting
protective mechanism of the Pt-nanozymes along lysosomal–mitochondrial
axes.