ACS applied materials & interfacesSep 29, 2026

A Brain-Targeted Nanoparticle System to Reduce Brain Inflammation After Stroke Using Combined Antioxidant and Anti-Inflammatory Actions

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 30, 2026

Abstract

TLNP@Pt/Fe3O4 reduced cerebral infarct and edema in a mouse model of transient middle cerebral artery occlusion (tMCAO).

The brain-targeted nanozyme system was developed to penetrate the blood-brain barrier effectively.
Pt/Fe3O4 nanozymes demonstrated stable multienzymatic activities and favorable biocompatibility.
In vitro, TLNP@Pt/Fe3O4 scavenged reactive oxygen species and reversed proinflammatory microglial polarization.
Improvement in neurological and spatial cognitive functions was observed with TLNP@Pt/Fe3O4 treatment.
The nanozyme regulated redox balance and inflammation via the PI3K/AKT signaling pathways.

Simplified

Ischemic stroke (IS) is severely aggravated by oxidative stress and neuroinflammation, while the blood-brain barrier (BBB) poses a major obstacle to effective therapy. Herein, we developed a brain-targeted nanozyme system (TLNP@Pt/Fe3O4) by encapsulating Pt/Fe3O4 nanozymes into T7 peptide-modified lipid nanoparticles. Pt/Fe3O4 exhibited stable multienzymatic activities (SOD/CAT/POD-like) and favorable biocompatibility. Mediated by T7 peptide targeting, the nanoparticle efficiently penetrated the BBB, enhanced cellular uptake in microglia, and reduced nontarget organ accumulation. In vitro experiments demonstrated that TLNP@Pt/Fe3O4 effectively scavenged reactive oxygen species (ROS), reversed proinflammatory microglial polarization, and inhibited neuronal apoptosis. In a mouse model of transient middle cerebral artery occlusion (tMCAO), TLNP@Pt/Fe3O4 alleviated cerebral infarct and edema, while improving neurological and spatial cognitive functions. Mechanistically, scRNA-Seq showed that the nanozyme synergistically regulated redox homeostasis and the inflammatory microenvironment through the PI3K/AKT signaling pathways. Integrating targeted delivery, multienzymatic catalysis, and multitarget regulation, TLNP@Pt/Fe3O4 provides a promising and translatable therapeutic strategy for IS.

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A Brain-Targeted Nanoparticle System to Reduce Brain Inflammation After Stroke Using Combined Antioxidant and Anti-Inflammatory Actions

Abstract

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