ACS Nano
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2025
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IF 16
Xianghua Zhong,Li Luo,Jiyuan Wu,Weirun Li,Xinyang Liu,Tenghui Ye,Zhenhua Li,Peng Shi
Mesenchymal stromal cell (MSC) therapy holds great promise for treating myocardial infarction (MI). However, the inflammatory and reactive oxygen species (ROS)-rich environment in infarcted myocardium challenges MSC survival, limiting its therapeutic impact. In this study, we demonstrate that chemical modification of MSCs with anti-VCAM1 and polydopamine (PD) significantly enhances MSC survival and promotes cardiac repair. Anti-VCAM1 modification facilitates MSC adhesion to inflamed tissue, ensuring MSC retention in the injured myocardium, while PD scavenges ROS surrounding MSCs, creating a conducive environment for cell transplantation. Our data indicate that chemically engineered MSCs effectively disrupt the inflammation-ROS cycle and modulate inflammation-related immune responses, thus improving MI microenvironments. Single-cell RNA sequencing of rat hearts reveals that treatment with engineered MSCs inhibits cardiac fibrosis by suppressing HB-EGF–EGFR signaling between anti-inflammatory macrophages and activated fibrillates. Ultimately, engineered MSCs demonstrate superior therapeutic efficacy in a rat model of MI. This study presents a straightforward, safe, and efficient chemical method for enhancing MSC therapy.
研究领域:
再生医学
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心血管病学
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细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Siqing Zhu,Yu Zhang,Chang Li,Zhiqing Deng,Ying Yin,Zhufeng Dong,Lei Kuang,Chuanming Li,Xiaoye Hu,Tieying Yin,Yazhou Wang
Aging is a critical factor in the onset and progression of neurodegenerative diseases and cognitive decline, with aging-related neuroinflammation and cellular senescence being major contributors. In the aging brain, the cerebral vascular endothelium overexpresses vascular cell adhesion molecule 1 (VCAM1), activating microglia and leading to neuroinflammation and cognitive impairment. Quercetin, a natural neuroprotective agent widely used for treating neurodegenerative diseases, their therapeutic efficacy, however, is limited by its poor water solubility and inability to penetrate the blood-brain barrier (BBB). To address these challenges, we developed a multifunctional micellar platform (Anti-VCAM1-GM1@Q) to improve age-related neurodegenerative diseases. The micelles incorporate anti-VCAM1 antibodies to target cerebral vascular endothelial cells and block VCAM1. Additionally, monosialoganglioside (GM1) was utilized to deliver quercetin due to its biparental properties, high BBB permeability, and neuroprotective effects. Anti-VCAM1-GM1@Q micelles demonstrated strong anti-aging properties. They improved quercetin's bioavailability, effectively penetrated the BBB, targeted cerebral vascular endothelial cells, and reduced neuroinflammation. In animal models, these micelles provided effective neuroprotection, improved memory function and age-related cognitive impairment, and mitigated age-related neurodegeneration. Notably, this system exhibited remarkable treatment efficacy and high safety, indicating substantial potential for clinical translational applications.
研究领域:
神经科学
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药理学
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衰老研究
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纳米技术
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2024
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IF 4.6
Chenming Zou,Ruihua Cai,Yunbing Li,Yu Xue,Guoguang Zhang,Gulimiran Alitongbieke,Yutian Pan,Sanguo Zhang
Recently, increasing evidence has shown the association between liver abnormal inflammation and cognition impairment, yet their age-related pathogenesis remains obscure. Here, our study provides a potential mechanistic link between liver macrophage excessive activation and neuroinflammation in aging progression. In aged and LPS-injected C57BL/6J mice, systemic administration of β-chitosan ameliorates hepatic macrophage-driven inflammation and reduces peripheral accumulations of TNF-α and IL-1β. Downregulation of circulatory pro-inflammatory cytokines then decreases vascular VCAM1 expression and neuroinflammation in the hippocampus, leading to cognitive improvement in aged/LPS-stimulated mice. Interestingly, β-chitosan treatment also exhibits the beneficial effects on the behavioral recovery of aged/LPS-stimulated zebrafish and Caenorhabditis elegans . In our cell culture and molecular docking experiments, we found that β-chitosan prefers shielding the MD-2 pocket, thus blocking the activation of TLR4-MD-2 complex to suppress NF-κB signaling pathway activation. Together, our findings highlight the extensive therapeutic potential of β-chitosan in reversing aged-related/LPS-induced cognitive impairment via the liver-brain axis.
研究领域:
免疫学
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神经科学
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老年学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Tong Yu,Yeqing Wang,Yi Kong,Jianwei Wang,Hong Yun,Yunchao Wang,Fuqiang Hu,Zhongxin Zhu,Hong Yuan
Drug delivery system (DDS) is an important branch of pharmaceutics. Rational modification of the physicochemical properties of DDSs can further improve their targeting efficiency. Herein, a bionic DDS is reported for AKI that is scRNA-seq-guided, custom-designed, and prepared, targeting the Key Cell Subtype for Pathological Progression (KCS-PP) of acute kidney injury (AKI). Specifically, scRNA-seq is utilized to identify a specific renal tubular epithelial cell subtype (PTIs) as the KCS-PP for AKI from numerous cellular subtypes. Additionally, specific cell adhesion molecules (VCAM1 and ICAM1) are identified as the Targeting Drug Delivery Mediators (TDDMs) for PTIs from a list of 1000 marker genes of PTIs. Based on this progress, PTI-targeting bionic DDS, named BRNCs@AMMOs is custom-designed and prepared, and used them for AKI treatment in vitro and in vivo. In vitro, BRNCs@AMMOs shows that its adhesion ability in PTI model cells is 3.2 times that in normal cells. In vivo, 6 h after renal pelvis injection, the MFI of BRNCs@AMMOs-DiI in AKI kidneys is 3.7 times that of sham kidneys. The findings demonstrate that BRNCs@AMMOs exhibits prolonged retention in PTI model cells and AKI kidneys. Overall, the custom-designed and prepared PTI-targeting bionic DDS, may promote the customized design and preparation of DDSs for different diseases and targets, is reported.
研究领域:
药剂学
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药物递送
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分子医学
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纳米技术
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）