Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage DOI
Sahily Reyes‐Esteves,

Aparajeeta Majumder,

Nicolas Marzolini

et al.

Published: April 8, 2025

Abstract Intracerebral hemorrhage (ICH) is a lethal and highly morbid form of stroke for which there no disease-specific therapy. Inflammation after ICH an important mechanism secondary damage, the inflamed endothelium in promising therapeutic target as it gateway inflammation brain. Systemic therapies that have been unsuccessful stroke, part due to side effects or poor brain delivery. We hypothesized targeting mRNA encoding IL-10, potent anti-inflammatory cytokine, vasculature would improve outcomes experimental mouse model ICH. manufactured lipid nanoparticles (LNPs) using microfluidics, packaged them with IL-10 mRNA, decorated antibodies against vascular cellular adhesion molecule (VCAM), can bind VCAM LNPs distributed ~4x more than nonspecific expressed their cargo at 10x higher levels. Treatment VCAM-LNPs containing led ~69% reduction hematoma size 72 hours ~65% improvement motor behavior our model, leakage. Finally, we observed primarily infiltrated macrophages neutrophils. VCAM-IL10-LNPs significantly increased plasma levels IL10. Our data provide preliminary delivery strategy ICH, shed light on relationship between Future experiments will seek understand how serial dosing affects LNP expression whether treatment later time points still confer effects.

Language: Английский

Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage DOI
Sahily Reyes‐Esteves,

Aparajeeta Majumder,

Nicolas Marzolini

et al.

Published: April 8, 2025

Abstract Intracerebral hemorrhage (ICH) is a lethal and highly morbid form of stroke for which there no disease-specific therapy. Inflammation after ICH an important mechanism secondary damage, the inflamed endothelium in promising therapeutic target as it gateway inflammation brain. Systemic therapies that have been unsuccessful stroke, part due to side effects or poor brain delivery. We hypothesized targeting mRNA encoding IL-10, potent anti-inflammatory cytokine, vasculature would improve outcomes experimental mouse model ICH. manufactured lipid nanoparticles (LNPs) using microfluidics, packaged them with IL-10 mRNA, decorated antibodies against vascular cellular adhesion molecule (VCAM), can bind VCAM LNPs distributed ~4x more than nonspecific expressed their cargo at 10x higher levels. Treatment VCAM-LNPs containing led ~69% reduction hematoma size 72 hours ~65% improvement motor behavior our model, leakage. Finally, we observed primarily infiltrated macrophages neutrophils. VCAM-IL10-LNPs significantly increased plasma levels IL10. Our data provide preliminary delivery strategy ICH, shed light on relationship between Future experiments will seek understand how serial dosing affects LNP expression whether treatment later time points still confer effects.

Language: Английский

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