Related Experiment Video
Updated: Sep 2, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Targeting microglia-mediated neuroinflammation via pH-responsive lipid nanoparticle delivery of HDAC inhibitor
1Department of Cerebrovascular Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Abstract:
Ischemic stroke (IS) remains a leading cause of global disability and mortality, with limited effective anti-inflammatory interventions. Targeting histone deacetylase 3 (HDAC3) to reprogram microglial polarization holds great therapeutic promise, but the HDAC3-specific inhibitor RGFP966 suffers from poor blood-brain barrier (BBB) penetration and systemic toxicity. Herein, we developed a pH-responsive brain-targeted lipid nanoparticle (CD-TLNP@RGFP966) by integrating T7 peptide modification for BBB transcytosis and cinnamaldehyde-α-cyclodextrin (CA-αCD) encapsulation for acidic lesion-triggered drug release. CD-TLNP@RGFP966 exhibited favorable colloidal stability, biosafety, and pH-dependent release behavior. It efficiently crossed the BBB, accumulated in ischemic brain tissue, promoted microglial M2 polarization, attenuated neuroinflammation, reduced infarct volume, and improved neurological function in tMCAO mice. This study provides a novel targeted nanocarrier strategy for the anti-inflammatory treatment of IS.
