SPARC-Targeted ZnS/BSA Nanoparticles For Multi-Mechanistic Mitigation of Early Brain Injury after Subarachnoid Hemorrhage

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Publication Details

Journal
ACS Applied Materials & Interfaces
Published
2026-09-04
DOI
https://doi.org/10.1021/acsami.6c09755
Primary Topic
Intracranial Aneurysms: Treatment and Complications
Type
article
Field-Weighted Citation Impact
0.00

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article

SPARC-Targeted ZnS/BSA Nanoparticles For Multi-Mechanistic Mitigation of Early Brain Injury after Subarachnoid Hemorrhage

Xishu Liu, Yue Yang, Yupeng Wang, Yucheng Chen et al.
ACS Applied Materials & Interfaces
Intracranial Aneurysms: Treatment and Complications
article

SPARC-Targeted ZnS/BSA Nanoparticles For Multi-Mechanistic Mitigation of Early Brain Injury after Subarachnoid Hemorrhage

Xishu Liu, Yue Yang, Yupeng Wang, Yucheng Chen, Hongjiang Liu, Xiaofeng Sun, Wei Wang, Hongyang Cheng, Lina Wang, Jipeng Yang, Chen Li
article en

Abstract

Subarachnoid hemorrhage (SAH) remains a devastating stroke subtype with high morbidity and mortality, largely due to complex early brain injury (EBI) within the first 72 h involving cerebral vasospasm (CVS), oxidative stress, and neuroinflammation. Existing therapies such as nimodipine offer limited protection and fail to address multiple injury pathways. Here, we report a SPARC-targeted albumin-based zinc sulfide nanoparticle (ZnS/BSA NPs) designed for lesion-specific delivery and multi-mechanistic therapy for SAH. We demonstrate that SPARC is significantly upregulated in both human and rat SAH brains, enabling active targeting of injured vasculature and crossing the blood-brain barrier (BBB). ZnS/BSA NPs exhibit good colloidal stability in serum-containing medium and pH-responsive release of Zn2+ and H2S. Mechanistically, Zn2+ suppresses Ca2+ influx/CaMKII activation to alleviate CVS; H2S activates NRF2/HO-1 to scavenge reactive oxygen/nitrogen species (RONS) and inhibits NF-κB/NLRP3 signaling to shift microglia from M1 to M2 polarization. Additionally, the NPs inhibit Caspase-1/GSDMD-mediated pyroptosis in microglia and suppress both Caspase-1/GSDMD-mediated pyroptosis and Bax/Caspase-3-mediated apoptosis in neurons, thereby preserving BBB integrity and reducing brain edema. In a rat SAH model, ZnS/BSA NPs significantly improved learning, memory, and motor function, outperforming nimodipine. This work highlights SPARC as a viable druggable target and represents a "targeted, multi-mechanistic" nanotherapeutic paradigm for EBI after SAH.

ACS Applied Materials & Interfaces
Hebei Medical University (CN), Kunming Medical University (CN), Second Hospital of Hebei Medical University (CN), Hebei Normal University (CN)
Health Commission of Hebei Province, Jiangsu Hengrui Medicine, National Natural Science Foundation of China, Natural Science Foundation of Hebei Province
Good health and well-being
Openalex Percentile: Top 11%
Intracranial Aneurysms: Treatment and Complications
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