Dataset Information

In Situ Proliferating Peptide Nanoparticle Augments Multi-Target Intervention of Secondary Brain Damage Following Subarachnoid Hemorrhage.

ABSTRACT: Subarachnoid hemorrhage (SAH), a lethal stroke subtype, involves complex pathological cascades triggered by neuro-glial units for persistent neuroinflammation, oxidative damage and programmed neuronal cell death. Single-target and traditional multi-target therapies, derived from individual drugs, show limited efficacy in addressing these interconnected events, due to spatiotemporal heterogeneity of action in single-target components. This highlights the urgent need for not only new therapeutic targets, but advanced multi-target drugs. Herein, we identify elevated cell-free DNA (cfDNA), a key neuroinflammatory driver, as correlated with SAH severity and poor prognosis, suggesting its therapeutic potential. Furthermore, a novel "in situ proliferation" strategy is proposed and a flexible multi-target peptide nanoparticle is developed through co-assembling matrix metalloproteinase-2 responsive cationic peptide and glutathione peroxidase-mimicking peptide (GPXP). Upon reaching injury lesions, this system splits into two individual drugs: cationic peptide scavenges pathological cfDNA and inhibits microglia-mediated neuroinflammation, while GPXP protects neurons against oxidative damage and neuronal apoptosis/ferroptosis. Consequently, this strategy proves superior therapeutic effects on reducing secondary brain injury and promoting neurofunctional recovery in SAH mice. These findings not only highlight the essential role of cfDNA in SAH but offer a flexible resolution to advance multi-target combinational therapy.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC12376667 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature

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In Situ Proliferating Peptide Nanoparticle Augments Multi-Target Intervention of Secondary Brain Damage Following Subarachnoid Hemorrhage.

Zhang Yibin Y Yao Peisen P Chen Fuxiang F Zheng Shufa S Niu Xuegang X Wang Haojie H Lin Yuanxiang Y Gao Bin B Kang Dezhi D

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20250530 31

Subarachnoid hemorrhage (SAH), a lethal stroke subtype, involves complex pathological cascades triggered by neuro-glial units for persistent neuroinflammation, oxidative damage and programmed neuronal cell death. Single-target and traditional multi-target therapies, derived from individual drugs, show limited efficacy in addressing these interconnected events, due to spatiotemporal heterogeneity of action in single-target components. This highlights the urgent need for not only new therapeutic t ...[more]

PMID: 40444439

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Project description:The diagnosis of cerebral vasospasm after Subarachnoid-Hemorrhage is currently very difficult, additional tools such as blood biomarkers are necessary. We tested the ability of gene expression profiles of blood cells to predict vasospasm. 32 patients suffering subarachnoid-hemorrhage were included in this prospective monocentre study. They were grouped according to have a complicated cerebral vasospasm (Vasospasm) or not (Control) and Paired according to age (+/- 10 years), sex, Fisher grade (+/- 1), location, smoking (at least 3 first parameters). Gene expression profiles of blood cells were determined using 25,000~gene microarray. Blood sample: 2.5 mL harvested in PAXgene® Blood RNA tubes (PreAnalytix) RNA extraction: PAXgene® Blood RNA kit (Qiagen). We used a Universel Reference RNA (Stratagene). RNA amplification and labelling: kit Amino Allyl MessageAmp II (Ambion). We hybridized 4 microarrays per patient using pangenomic microarrays from the "Réseau National des Génopôles" (Illkirch, France). 2 slides were hybridized with reference RNA labelled Cy3 and patient RNA labelled Cy5, and 2 slides were hybridized with reference RNA labelled Cy5 and patient RNA labelled Cy3. Hybridation : Agilent protocol with few modifications : 750 ng of each labelled RNA were hubriddized at 60°C during 17 hours in an Aglient hybridization oven. After washings, Slides were scanned with a GenePix 4000B scanner (Molecular Devices). Image intensity data were extracted with GenePix Pro 6.0 analysis software. Quantification of Cy3 and Cy5 and selection of good spots were performed using the MAIA software (Novikov E and Barillot E. Software package for automatic microarray image analysis (MAIA). The ACUITY software was then used to normalize log ratios Cy3/Cy5 with Lowess non linear normalization, to filter out genes not present in at least 3 slides out of 4, to evaluate the reproducibility of the 4 microarrays of each patient (hierarchical clustering, Self Organizing Maps). Statistical analyses to insure reproducibility was performed using Excel (correlation coefficients, ANOVA). Only slides that passed all reprocubility tests were validated.

Dataset Information

In Situ Proliferating Peptide Nanoparticle Augments Multi-Target Intervention of Secondary Brain Damage Following Subarachnoid Hemorrhage.

Publications

In Situ Proliferating Peptide Nanoparticle Augments Multi-Target Intervention of Secondary Brain Damage Following Subarachnoid Hemorrhage.

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