Enhancing Drug Delivery and Efficacy in Stroke via Supramolecular Nanoparticle Systems
4 affiliations
- 1Yangzhou University , , ,
- 2Yangzhou University Affiliated Taixing Hospital , , ,
- 3Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese and Western Medicine in Senile Diseases Control (Yangzhou University) , ,
- 4Changzhou Center for Disease Control and Prevention , ,
Abstract
The pathogenesis of ischemic stroke involves multiple pathological links, such as blood–brain barrier (BBB) disruption, oxidative stress, and neuroinflammation, making comprehensive intervention via a single drug exceedingly difficult. In this study, we constructed a supramolecular coassembly nanoparticles (UA-Gen NPs) composed of Ursolic acid (UA) and Genistein (Gen), which self-assemble into a stable supramolecular structure driven by intermolecular hydrogen bonding and π-π stacking. This nanoplatform not only significantly improved drug hydrophilicity but also achieved a transformation from simple physical mixing to structural integration. In vitro profiles revealed a distinct pH-responsive and sequential release pattern of the system (“fast-Gen/slow-UA”). Pharmacokinetic studies further demonstrated that this coassembly significantly prolonged blood circulation and synchronized the fates of the two drugs in vivo. In a mouse middle cerebral artery occlusion (MCAO) model, UA-Gen NPs exhibited superior efficacy in alleviating BBB leakage, reducing infarct volume, and improving neurobehavioral outcomes compared to their physical mixture. Serological analyses confirmed its regulation of oxidative stress and systemic inflammation, yielding optimal neuroprotection. At the protein expression level, the nanotherapy significantly inhibited Keap1, upregulated Nrf2, and restored Occludin expression. Altogether, by utilizing drug molecules themselves as structural building blocks, this study engineered a supramolecular nanotherapeutic agent featuring microenvironment-responsive release behavior and sequential drug delivery. This work provides a feasible research strategy to overcome the challenges of combination therapy in complex diseases.
Related
- Supramolecular structuring of nanoparticle ligand shells revealed by liquid-phase AFM
- Dendritic Mesoporous Silica Nanoparticle-Based Co-Delivery of a Repellent and an Insecticide for Management of the Asian Citrus Psyllid
- A dual-targeting lipid nanoparticle delivery system for precision phage therapy against multidrug-resistant Gram-negative bacteria
- Development of Versatile Nanoparticle System for Efficient Drug Delivery into Pulmonary Endothelium.
- Nanoparticle-Mediated Brain-Targeted Drug Delivery for Methamphetamine Use Disorder: Advances, Challenges and Translational Perspectives.
BibTeX
@article{huang2026enhancing,
title = {{Enhancing Drug Delivery and Efficacy in Stroke via Supramolecular Nanoparticle Systems}},
author = {Xing Yu Huang and Ming Yang Xu and Meng Zhang and Xin Lu and Jian Bin Tang and Bing Chun Yan and Jia Cheng Wang},
journal = {ACS Omega},
year = {2026},
month = oct,
doi = {10.1021/acsomega.6c04753},
url = {https://pubs.acs.org/acsodf/article/11/42/64673/5449779/Enhancing-Drug-Delivery-and-Efficacy-in-Stroke-via},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Enhancing Drug Delivery and Efficacy in Stroke via Supramolecular Nanoparticle Systems
AU - Xing Yu Huang
AU - Ming Yang Xu
AU - Meng Zhang
AU - Xin Lu
AU - Jian Bin Tang
AU - Bing Chun Yan
AU - Jia Cheng Wang
PY - 2026
DA - 2026/10/13
JO - ACS Omega
DO - 10.1021/acsomega.6c04753
UR - https://pubs.acs.org/acsodf/article/11/42/64673/5449779/Enhancing-Drug-Delivery-and-Efficacy-in-Stroke-via
AB - The pathogenesis of ischemic stroke involves multiple pathological links, such as blood–brain barrier (BBB) disruption, oxidative stress, and neuroinflammation, making comprehensive intervention via a single drug exceedingly difficult. In this study, we constructed a supramolecular coassembly nanoparticles (UA-Gen NPs) composed of Ursolic acid (UA) and Genistein (Gen), which self-assemble into a stable supramolecular structure driven by intermolecular hydrogen bonding and π-π stacking. This nanoplatform not only significantly improved drug hydrophilicity but also achieved a transformation from simple physical mixing to structural integration. In vitro profiles revealed a distinct pH-responsive and sequential release pattern of the system (“fast-Gen/slow-UA”). Pharmacokinetic studies further demonstrated that this coassembly significantly prolonged blood circulation and synchronized the fates of the two drugs in vivo. In a mouse middle cerebral artery occlusion (MCAO) model, UA-Gen NPs exhibited superior efficacy in alleviating BBB leakage, reducing infarct volume, and improving neurobehavioral outcomes compared to their physical mixture. Serological analyses confirmed its regulation of oxidative stress and systemic inflammation, yielding optimal neuroprotection. At the protein expression level, the nanotherapy significantly inhibited Keap1, upregulated Nrf2, and restored Occludin expression. Altogether, by utilizing drug molecules themselves as structural building blocks, this study engineered a supramolecular nanotherapeutic agent featuring microenvironment-responsive release behavior and sequential drug delivery. This work provides a feasible research strategy to overcome the challenges of combination therapy in complex diseases.
SN - 2470-1343
ER -