CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Yuan Zhong,Kai Qu,Wenhua Yan,Kun Zhang,Xian Qin,Yi Wang,Meng Yan,Shuai Wu,Li Zhu,Essam Abdo Mohammed Saad Obaid,Guixue Wang,Wei Wu
The development of atherosclerosis (AS) is closely related to inflammation. The common feature of inflammatory sites is upregulation of vascular cell adhesion molecule-1 (VCAM-1), which has a strong affinity with very late antigen-4 (VLA-4). Endothelial cell membranes overexpressing VLA-4 (OEM) were used to camouflage rapamycin nanoparticles (RAP NPs) with reactive oxygen species (ROS) responsiveness to construct biomimetic nanodrugs [email protected] NPs. These nanoparticles were capable of enhancing the active target drug delivery and ROS-responsive drug release under the pathological overexpression of VCAM-1 and accumulation of ROS stimulus. In vitro and in vivo investigations confirmed that [email protected] NPs could enhance the active target drug delivery to atherosclerotic plaques and increase drug accumulation in the focal site, thus improving the bioavailability of drugs, reducing side effects and inhibiting the occurrence and development of atherosclerosis.
研究领域:
药理学
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纳米技术
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心血管疾病
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产品关联
DOI
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Shuang Bian,Yangang Zhu,Nanxin Zhao,Yanchen Wang,Zhimou Yang,Jingjing Li
Atherosclerosis (AS) is characterized by lipid overaccumulation and progressive chronic inflammation. Macrophages over-accumulate at plaque sites and promote fibrous cap instability and plaque rupture by participating in lipoprotein uptake and metabolism, inflammatory factor secretion, and the production of enzymes and toxic metabolites. The macrophages accumulating at plaque sites are mainly derived from circulating blood-derived monocytes. Therefore, we designed a peptide 2P with an alkaline phosphatase (ALP) induced self-assembly function and P-selectin targeting function to form a supramolecular bi-antibodies 2P@VLA-4 by coassembling with VLA-4, a CD106 affinity. The dephosphorylation site and efficiency were optimized. 2P@VLA-4 displayed enhanced protein stability and binding ability to inflamed vascular endothelial cells. Through the dual-targeted blocking effect on the adhesion binding site of monocytes, 2P@VLA-4 could significantly reduce the accumulation of monocytes/macrophages at the plaque site, thereby inhibiting the progression of AS. At the same time, modification of peptides with fluorescent molecules enabled specific imaging of plaques. This study focused on the ease of design and functionalization of peptides, to synthesize supramolecular bi-antibodies compound innovatively by enzyme instructed self-assembly (EISA), achieving the significant inhibition of the adhesion and aggregation of monocytes at plaque sites. Coupling with its specific imaging capability, it may provide new approaches for the integrated design of diagnosis and treatment of AS .
研究领域:
医学
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生物化学
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纳米医学
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 21
·10773-10782
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IF 5.396
Ritian Jin,Haowei Ren,Minhe Liao,Jiaqi Shang,Dangfeng Wang,Meng Li,Ning Liu
The peptide VLATSGPG (VLA) is known to inhibit dipeptidyl peptidase IV (DPP-IV), although its mechanism in relieving endoplasmic reticulum (ER) stress is unclear. In this study, we found that treating HepG2 cells with 1.0 mM VLA reduced DPP-IV activity by 73.7 ± 4.8% without changing the DPP-IV mRNA expression level. In addition, 1.0 and 0.5 mM VLA alleviated palmitic acid (PA)-induced cell death and intracellular calcium imbalances. The levels of apoptosis-related proteins (caspase-3, caspase-9, and CHOP) were reduced by VLA treatment, which was presumed to be related to ER stress. Further studies confirmed that VLA alleviated PA-induced morphological damage to the ER and reduced the levels of the ER stress marker proteins (BIP, p-PERK, and p-IRE1α). VLA alleviated PA-induced ER stress in HepG2 cells independent of DPP-IV enzymatic activity inhibition. These findings have implications for developing novel treatment approaches for liver diseases caused by ER stress.
研究领域:
分子生物学
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细胞生物学
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药理学
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肝病
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产品关联
DOI
PubMed
高影响因子
Nano Today
·
2023
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IF 17.4
Honghui Wu,Xinchi Jiang,Yaosheng Li,Yunfei Dong,Juanjuan Zheng,Lu Li,Ying Li,Jinqiang Wang,Xianming Lin,Xiangnan Zhang,Tianyuan Zhang,Zhen Gu,Jianqing Gao
Blood-brain barrier (BBB) dis-integrity, a characteristic of extensive inflammatory encephalopathy, provides the access for brain-targeted drug delivery. Inspired from the bioresponsiveness of stem cell, we conceived of new nano-scale delivery strategy via neural stem cell membrane-derived bioresponsive vesicles (NSC-Lipo) for inflamed BBB target delivery. After recombination of neural stem cell membranes with simple liposomes , the functional ligands, especially very late antigen-4 (VLA-4), were entirely engrafted into NSC-Lipo and equipped the NSC-Lipo with “pass order” to the “selective gate”. It bestowed the bioresponsive vesicles with selective target the injured brain microvessel endothelial cells (BMECs) and penetrate into the lesion through the vascular cell adhesion molecule-1 (VCAM-1)/VLA-4 interaction in the post-ischemic mice model. The released anti-inflammatory agent, metformin , could reverse the inflammatory response of BMECs and rapidly recovers BBB’s integrity. With the repair of BBB’s integrity and down regulation of VCAM-1 expression, the targeting ability of bioresponsive vesicles cease to be in force as well. The bioresponsive vesicles led to enhanced survival rate of ischemic stroke mice (from 30 % to 90 %) after just a single injection compared to metformin loaded bare liposomes.
研究领域:
神经科学
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药剂学
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干细胞生物学
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药物递送系统
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产品关联
DOI
高影响因子
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