International Journal of Nanomedicine
·
2023
·
IF 8
Yuji Wang,Jingcheng Tang,Haimei Zhu,Xueyun Jiang,Jiawang Liu,Wenyun Xu,Haiping Ma,Qiqi Feng,Jianhui Wu,Ming Zhao,Shiqi Peng
The hot water extract of Rabdosia rubescens was traditionally used as an antithrombotic medicine. To explore its antithrombotic utility and mechanism, we carried out a series of in vitro and in vivo assays in this study. In vitro platelet aggregation assay showed that the half maximal inhibitory concentration values of aqueous extract of R. rubescens leaves (AERL) inhibiting platelet aggregation induced by thrombin, arachidonic acid, adenosine diphosphate, and platelet-activating factor ranged from 0.12 mg/mL to 1.43 mg/mL. The minimal effective oral dose of AERL inhibiting the rats from forming thrombus was 25 mg/kg. Both in vitro and in vivo actions were correlated with AERL concentration-dependently inhibiting sP-selectin release. In water, AERL formed nanoparticles, and their size depended on the concentration. Docking the five nucleotides, 21 phenolic acids, and four diterpenoids identified by high-performance liquid chromatography–photodiode array detector/(−)electrospray ionization-tandem mass spectrometry analysis into the active site of P-selectin, rosmarinic acid was predicted to be the antithrombotic ingredient of AERL. In flow cytometry analysis, 1 μM of rosmarinic acid effectively inhibited sP-selectin release in arachidonic acid-activated platelets. In a rat model, 5 mg/kg of oral rosmarinic acid effectively inhibited thrombosis.
研究领域:
药理学
·
分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Zhengjie Meng,Hao Wang,Xue Fang,Zhangya Liu,Zheng Yang,Jiahui Yong,Qingqing Yang,Yunhao Bai,Hao Ren,Hao Xu,Xueming Li
The vascular wall is the first physiologic barrier that circulating nanoparticles (NPs) encounter, which also is a key biological barrier to cancer drug delivery. NPs can continually scavenge the endothelium for biomarkers of cancer, and the chance of NPs’ extravasation into the tumors can be enhanced. Here, we envision P-selectin as a target for specific delivery of drug nanocrystals to tumors. The cupric diethyldithiocarbamate nanocrystals (CuET NCs) were first prepared by an antisolvent method, and then nanocrystals were coated with fucoidan via physical interaction. The fucoidan-coated CuET nanocrystals (CuET@Fuc) possess high drug loading and have the ability to interact with human umbilical vein endothelial cells expressing P-selectin, which transiently enhances the endothelial permeability and facilitates CuET@Fuc extravasation from the peritumoral vascular to achieve higher tumor accumulation of drugs than bare CuET NCs. The CuET NC shows poorer anticancer efficacy than CuET@Fuc at the same dose of CuET. Upon repeated dosing of CuET@Fuc for 2 weeks, no mortality was observed in treated melanoma-bearing mice, while the mortality in the control group and excipient-treated groups reached 23%. The growth rate of melanoma in the CuET@Fuc-treated group was significantly lower than those in other groups. Furthermore, an acute toxicity study revealed that CuET@Fuc is a safe formulation for cancer treatment.
研究领域:
药剂学
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肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Siya Wu,Xu Zhang,Jian Liu,Jianxi Song,Ping Yu,Peichao Chen,Zhiyong Liao,Mingjiang Wu,Haibin Tong
P-selectin, mediated adhesion between endothelium and neutrophils, is a promising target for the therapeutics of acute inflammatory-related diseases. It is reported that brown algal fucoidans can antagonize P-selectin function. However, the fractionation and physicochemical characterization of Sargassum fusiforme fucoidan, and the screening of fucoidan fractions with P-selectin antagonistic capability have not been investigated. In this study, we isolated and fractionated systematically the S. fusiforme fucoidan by ion-exchange chromatography and size exclusion chromatography to obtain eight fucoidan fractions. Their physicochemical characterization was determined by chemical methods, HPLC and FT-IR. The inhibitory capacity of the fucoidan fractions in P-selectin-mediated leukocyte adhesion was evaluated by static adhesion assay and parallel-plate flow chamber. Results showed that fucoidan fractions possessed distinct physicochemical properties, including total carbohydrate, uronic acid and sulfate contents, molecular weight, and monosaccharide compositions. Among all the fucoidan fractions, SFF-32 and SFF-42 showed better blocking ability against P-selectin-mediated cell adhesion.
研究领域:
海洋生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Ying Pan,Huifang Sun,Xi Gu,Sujuan Li,Shengtao Yang,Liang Zhang,Hui Mao,Pin Wang,Shasha Yang,Ronghua Yin,Zhili Zuo,Jinhua Zhao
Fucosylated chondroitin sulfate (FCS) from Holothuria mexicana (FCS Hm ) was selected for investigation because of its intriguing branch features. Selective β-eliminative depolymerization and the bottom-up assembly were performed to unravel that FCS Hm consisted of a {D-GlcA-β1,3-D-GalNAc 4S6S } backbone and branches of alternating Fuc S (55 %) and D-GalNAc S -α1,2-L-Fuc S (45 %), the highest proportion of disaccharide branch reported to date. In branches, sulfation could occur at every free -OH site except O-3 of GalNAc, being the most complex and various structure features of natural FCS. Detailed structure-activity relationship analyses showed that FCS Hm and its depolymerized products (>8 kDa) effectively competed with SLe X and PSGL-1 to bind with P-sel at nano-molar level and the inhibition potency increased with Mw increasing. For the structural trisaccharide unit, di-O-sulfation of the Fuc S (Fuc 2S4S and Fuc 3S4S ) was almost 10-fold more potent than mono-O-sulfation (Fuc 4S ). Unexpectedly, higher sulfation of the disaccharide-branched tetrasaccharide unit reduced inhibition. The reversal may attribute to fewer interactions with P-sel by molecular docking study. These results suggested that the specific configuration underpinned the potent inhibition, whereas the size and sulfate number of branches were not the key factors for the specific binding. d Hm F4 (8.0 kDa) potently blocked the platelet-leukocyte aggregates formation, further verifying the potential value in use.
研究领域:
海洋生物化学
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
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
·
生物化学
·
纳米医学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Dingfu Wang,Dan Li,Xiaolin Liu,Shixin Wang,Yile Fan,Ling Lu,Chuanbin Shen,Chunxia Li
Thrombolytic therapy for cardiovascular and cerebrovascular diseases is significantly limited by the short half-life, inadequate targeting specificity, and hemorrhagic complications of conventional therapeutic agents. To overcome these challenges, we developed a dual-functional nanogel (PGS-SP@UK) that integrates P-selectin-mediated thrombus targeting with ROS-responsive drug release. Taking advantage of the P-selectin targeting capability of polyguluronate sulfate (PGS), we synthesized the sulfated polysaccharide with selenocystamine and pinacol phenylboronate (PBAP) to construct an amphiphilic copolymer capable of encapsulating urokinase (UK). Notably, this nanogel exhibited H 2 O 2 -triggered UK release (85.79%) while maintaining great stability under physiological conditions. In vitro studies confirmed its neuroprotective effects through modulation of the ferroptosis signaling pathway in an OGD/R-induced model. In vivo studies revealed efficient blood-brain barrier penetration and thrombus-specific accumulation, achieving 84.3% recovery in cerebral infarct area through synergistic thrombolysis and oxidative stress mitigation. Our study presents an innovative drug delivery system with significant potential for clinical ischemic stroke treatment. Statement of Significance Conventional thrombolytic agents suffer from poor targeting specificity and severe bleeding complications, limiting their clinical efficacy in ischemic stroke treatment. We designed a dual-functional nanogel (PGS-SP@UK) that uniquely integrates P-selectin-mediated active targeting with ROS-responsive drug release mechanisms. This innovative design represents a system to combine polyguluronate sulfate-based thrombus recognition with oxidative stress-triggered urokinase liberation. Our nanogel achieves unprecedented selectivity through dual targeting: bioactive targeting via P-selectin binding and microenvironmental responsiveness to pathological ROS levels. In vivo validation demonstrated exceptional therapeutic outcomes with 84.3% cerebral infarct recovery while eliminating systemic hemorrhagic risks. This breakthrough establishes a new therapeutic paradigm that transcends current limitations through synergistic thrombolysis and neuroprotection, offering transformative potential for precision medicine in thrombotic disorders.
研究领域:
生物材料
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纳米医学
·
脑血管病学
·
药物递送系统
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氧化应激
·
神经保护
·
血栓靶向
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Huijuan Zhang,Yingmei Tian,Yan Ren,Yaning Wang,Chaoqun Wang,Lin Hou
Inflammatory infiltration and lipid metabolism disorder are two main characteristics of atherosclerosis (AS) plaque microenvironment. They interact to form a malignant positive feedback cycle, which aggravates the development of AS disease. Therefore, simultaneous improvement of inflammation and lipid metabolism will provide a significant therapeutic effect on AS. To achieve this goal, we first prepared FCD (Fuc-TK-CD) by grafting β-cyclodextrin (β-CD) to fucoidan (Fuc) via reactive oxygen species (ROS)-responsive sulfhydryl disulfide bond (TK), then loaded resveratrol (Res) through the host-guest interaction. Finally, we coated it on the surface of SeNPs through Se O bonds to obtain FCD-Se/Res nanoplatforms. FCD-Se/Res can actively recognize P-selectin and penetrate the AS plaque interior. Subsequently, FCD-Se/Res responded to the high shear force and abundant cholesterol in the plaque microenvironment to release Res, reducing AS plaque inflammation by reversing M1 macrophages to M2 phenotype. Meanwhile, TK bonds broke in response to high ROS levels in the plaque, making β-CD free to clear excessive pathogenic cholesterol from plaques. Benefiting from the integrated multifunctionality, FCD-Se/Res can break the vicious cycle between inflammation and disrupted lipid metabolism, jointly stabilize vulnerable plaques, and exert efficient anti-AS effects. The pharmacodynamic results revealed a significantly reduced plaque vulnerability index (VI) from 4.07 to 0.40 after FCD-Se/Res treatment.
研究领域:
生物医学工程
·
药剂学
·
心血管病学
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Gaofeng Shu,Lin Shen,Jiayi Ding,Junchao Yu,Xiaoxiao Chen,Xiaoju Guo,Enqi Qiao,Yaning Chen,Chenying Lu,Zhongwei Zhao,Yongzhong Du,Minjiang Chen,Jiansong Ji
The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd 3+ /DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd 3+ /DOX had a high photothermal conversion efficiency of 33.4% and excellent T 1 −MRI performance with a longitudinal relaxivity (r 1 ) value of 14.966 mM −1 · s − 1 . Moreover, the results suggested that FMPDA/Gd 3+ /DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd 3+ /DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd 3+ /DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics
研究领域:
纳米技术
·
癌症治疗
·
医学影像
·
药学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2019
·Vol. 10
·期 6
·3379-3385
·
IF 3.241
Qi Chen,Hongxia Yang,Yan Li,Xiaoxi Wang,Lixin Wei,Yuzhi Du
Studies have shown that gelatin is not only a good hemostatic material, but also a food additive with potentially broad use. Yak skin gelatin is a new gelatin resource, but its oral coagulant effects have not been studied. Given the central role of platelets in hemostasis, in this study we examined the pharmacodynamical differences between different molecular Yak skin gelatins on platelet activation. The hemostatic effects of Yak skin gelatins with different molecular weight distributions were evaluated for bleeding time (BT), clotting time (CT), and platelet activity by measuring the contents of P-selectin, platelet membrane glycoprotein Ia/IIa (GP Ia/IIa), platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa), and platelet membrane glycoprotein IV (GP IV). Intragastric administration of Yak skin gelatin resulted in a significant reduction in CT and BT, and an increase in the contents of P-selectin, GP Ia/IIa, GP IIb/IIIa, and GP IV in all groups in comparison with the control group. The strongest activation of platelets by Yak skin gelatin was observed with size between 0.1 μm and 0.22 μm, and activation may have been in response to improving GP IIb/IIIa and GP IV levels. When measuring the levels of an established indicator of platelet activation, platelet activation-dependent granule membrane protein (CD62P), its promotion was observed for all molecular weight ranges of Yak skin gelatins. In brief, Yak skin gelatin has hemostatic effects, and Yak skin gelatin fractions between 0.1 μm and 0.22 μm are the primary effectors of hemostasis via promoting platelet membrane glycoprotein activities and strengthening platelet function.
研究领域:
药理学
·
止血
·
血小板功能
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 13
·1806620
·
IF 15.621
Yujie Zhang,Xi Zhu,Xinli Chen,Qinjun Chen,Wenxi Zhou,Qin Guo,Yifei Lu,Chao Li,Yu Zhang,Donghui Liang,Tao Sun,Xunbin Wei,Chen Jiang
The frequent relapse and metastasis characteristics of triple negative breast cancer (TNBC) make it a fraught issue with very poor prognosis in clinic. An effective treatment for TNBC should prevent and even eliminate metastasis as well as suppress primary lesion expansion. Recent progress reveals that platelets can be recruited and activated by tumor cells through intercellular adhesion molecules (ICAM), and help aggressive circulating tumor cells (CTCs) form metastasis. Therefore, activated platelets are considered with possession of tumor-homing, CTC-capturing, and metastasis-targeting abilities. In this work, a P-selectin (expressed on activated platelet surface) targeting peptide (PSN) is modified on a redox-responsive paclitaxel-loaded micelle (PSN-PEG-SS-PTX 4 micelle) to utilize activated platelets as a “bridge” for interaction with cancer cells. The PSN-modified micelle can easily adhere to the surface of activated platelets and subsequently capture CTCs in blood circulation. Compared to Taxol and PEG-SS-PTX 4 micelle, PSN-PEG-SS-PTX 4 micelle also exhibits enhanced primary TNBC/metastasis targeting and penetrating effect through binding with tumor infiltrating platelets and thus significantly improves treatment outcome. More importantly, PSN-PEG-SS-PTX 4 micelle potently suppressed lung metastasis of TNBC and reduced incidence of distant liver metastasis. The activated platelet-targeting redox-responsive micelle system provides a promising prospect for the omnidirectional treatment of metastatic cancer.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
癌症生物学
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产品关联
DOI
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Ying Wang,Chuanjiang Jian,Yiqing Long,Xiaowen Xu,Yang Song,Zongning Yin
Pathological coagulation within an injured artery and the subsequent cardiovascular complications, such as stroke and heart attack, greatly threaten human life. Inspired by the biochemical features of acute arterial thrombosis, such as abundant activated platelets and hydrogen peroxide (H 2 O 2 ), we constructed platelet-targeted theranostic nanoparticles (CyBA/PFM NPs) with H 2 O 2 -triggered photoacoustic contrast enhancement and antithrombotic capabilities. CyBA/PFM NPs were designed to target platelet-rich clots via fucoidan segment within the carrier, which could be activated by H 2 O 2 to produce fluorescent “CyOH” molecules, thus turning on the photoacoustic signal. CyBA/PFM NPs showed obvious amplification of fluorescence following incubation with fresh clots, exhibiting efficient scavenging ability of intracellular reactive oxygen species (ROS). In a FeCl 3 -induced mouse model of carotid thrombosis, CyBA/PFM NPs significantly amplified the photoacoustic contrast in thrombogenic tissues, effectively eliminated ROS within the occlusion site, and suppressed the thrombus formation , accompanied by a normalization of the soluble CD40L level. Given their accurate imaging potential, potent antithrombotic activities and acceptable biosafety, CyBA/PFM NPs hold strong potential as nanoscale theranostics for H 2 O 2 -correlated cardiovascular diseases. Statement of significance In this study, we developed a platelet-targeted and H 2 O 2 -triggered nanosystem self-assembled from phenylboronated fucoidan/maltodextrin polymers and responsive near-infrared probes. The fucoidan segment within the carrier could facilitate the specific delivery of the therapeutic polymers and probes to the platelet-rich arterial thrombus. In a mouse model of FeCl 3 -induced arterial thrombosis, the system could be activated by H 2 O 2 to produce fluorescent “CyOH” molecules, thus turning on the photoacoustic signal and specifically imaging thrombosed tissues. Besides, CyBA/PFM NPs significantly effectively eliminated ROS within the occlusion site and suppressed the thrombus formation. Given their theranostic potential and acceptable biosafety, this system has great potential for H 2 O 2 -correlated cardiovascular diseases.
研究领域:
纳米技术
·
生物医学工程
·
心血管疾病
·
诊疗一体化
·
分子影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Dingfu Wang,Xiaolei Qiu,Lihua Hao,Zirui Fan,Shixin Wang,Chunxia Li
The exploration of efficient and safe chemodynamic therapy (CDT)-based cancer treatment is expected but still faces challenges. Herein, a kind of multifunctional nanomicelles was constructed for CDT, combined with biocompatible polysaccharides as nanocarriers, pH responsiveness and active targeting of P-selectin overexpressed tumors. The P-selectin-targeted ligand, polyguluronate sulfate (PGS), complexed with copper peroxide to form PGS-Cu nanomicelles by electrostatic interactions. Under acidic conditions, PGS-Cu nanomicelles released copper ions with H 2 O 2 and were able to produce •OH by Fenton-like reaction. In vitro data demonstrated PGS-Cu nanomicelles had high selectivity targeting P-selectin over-expressed cancer cells and induced cell death via CDT. In vivo evaluation showed PGS-Cu nanomicelles were enriched in tumor tissues and significantly inhibited tumor growth. This study identified that PGS-Cu nanomicelles could be a highly effective strategy for CDT cancer treatment.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 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）