INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Biyun Lan,Junfeng Wu,Na Li,Chenglin Pan,Li Yan,Chuan Yang,Liming Zhang,Liqun Yang,Meng Ren
Gene vectors are important for successful siRNA delivery. Four types of hyperbranched cationic polysaccharide derivatives (HCP) were synthesized by conjuncting 1,2-ethylenediamine (EDA) and diethylenetriamine (DETA) with glycogen or amylopectin respectively and named as G-EDA, G-DETA, A-EDA and A-DETA. The efficiency and safety of these HCPs to deliver siRNA were explored in vitro and in vivo . Our results showed that HCPs could form complexes with siRNA. All HCP/siRNA exhibited negligible cytotoxicity. Compared with A-EDA and A-DETA, G-EDA and G-DETA could carry much more siRNA into cells and then escape from endosomes. The delivery of MMP-9 siRNA (siMMP-9) by G-EDA and G-DETA significantly inhibited MMP-9 in HaCaT cells. Wound models in diabetic rats demonstrated that treatment of G-EDA/siMMP-9 could potently knock down MMP-9 of skin wound tissues and then enhanced wound healing. In summary, this study provided an effective and safe approach for siRNA delivery in vitro and in vivo .
研究领域:
药学科学
·
生物技术
·
伤口愈合
·
糖尿病研究
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纳米技术
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基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 13
·2573-2588
·
IF 5.344
Jintian Chen,Hui Wang,Liling Mei,Bei Wang,Ying Huang,Guilan Quan,Chao Lu,Tingting Peng,Xin Pan,Chuanbin Wu
A deep partial thickness (DPT) burn injury refers to burn damage involving the epidermis and major dermis, whose prognosis depends greatly on wound management. Lack of effective management can lead to an elongated healing process and aggravated scar formation, which can severely disturb patients, both physically and mentally. A dressing with good water absorption and moderate mechanical properties is crucial for healing promotion, and the prevention of scar formation is highly desirable. In this project, a hyaluronic acid combined lyotropic liquid crystal based spray dressing (HLCSD) loaded with the anti-fibrotic drug pirfenidone (PFD) has been designed. HLCSD is expected to achieve the goals of both wound healing promotion and scar prophylaxis. Its water absorption capacity, mechanical properties, drug release behavior and phase transition are fully evaluated. HLCSD possesses low viscosity for spray administration and high levels of water absorption for exudate absorption. An in situ gel composed of self-assembled lattice nanostructures provides excellent mechanical protection to promote the healing process and steady PFD release to exert a scar prophylaxis effect. The benefit of HLCSD on the wound healing rate is verified in vivo. In the DPT burn wound model we established, HLCSD also exhibits excellent healing promotion effects, and PFD-loaded HLCSD shows scar prophylaxis effects and displays an ideal prognosis, with skin as smooth as healthy skin. The healing promotion of HLCSD is considered to be related to the alleviation of inflammation, with an obviously shortened inflammation phase, with contributions from water management, mechanical protection and anti-inflammation by HLCSD. The scar prophylaxis of PFD-loaded HLCSD is proven to be related to the regulation of collagen synthesis and degradation, involving key cytokines like TGF-β and MMP-1. Taken together, the PFD-loaded HLCSD with healing promotion and scar prophylaxis offers significant promise as a spray dressing for DPT burn injuries.
研究领域:
药剂学
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生物医学工程
·
伤口愈合
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烧伤治疗
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2016
·Vol. 12
·期 31
·4286-4298
·
IF 8.315
Qi Lei,Wen-Xiu Qiu,Jing-Jing Hu,Peng-Xi Cao,Cheng-Hui Zhu,Han Cheng,Xian-Zheng Zhang
In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG-generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host–guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Fan Yang,Gaoyang Guo,Yunbing Wang
Cardiovascular implants made from heterogeneous tissues (HT) often clinically face premature failures such as thrombosis, inflammation, and calcification. Herein, we report a hydrogel-tissue composite exhibiting inflammation instructive release of multiple components towards preventing coagulation, promoting endothelial growth, and modulating reactive oxygen species (ROS) homeostasis . The hydrogel composed of MMP-responsive segment-crosslinked heparin mimicking polymer was loaded with a nitroxide radical via ROS cleavable boronic ester bonds and vascular endothelial growth factor (VEGF) via electrostatic attraction . Matrix metalloproteinase (MMP), which reportedly showed elevated expression in inflammation response to foreign implant degraded the hydrogel and led to the release of heparin mimicking polymer and VEGF, enhancing its anti-coagulation capacity and accelerating the growth of endothelial cells on it. In addition, the composite could sense oxidation biosignal present in the inflammation environment and subsequently release a ROS scavenger for auto-regulation of ROS balance. Subcutaneous implantation in mice suggested that the composite could steer the immune response toward an anti-inflammation state and subcutaneous implantation in rats suggested an anti-calcification effect of it. The enhanced hemocompatibility and endothelialization effects in vivo were further confirmed by the endovascular implantation of tissues via membrane-covered stent delivery. The current findings demonstrate that the incorporation of functional hydrogel into the tissue sophistically exploiting host response for controlled release of multiple active cargos is a feasible approach to boost the anticoagulant, endothelialization, anti-inflammatory, and anti-calcification functions of HT-based cardiovascular implants.
研究领域:
生物材料
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组织工程
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心血管科学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Yeping Wu,Anzhi Wang,Xiaokang Ding,Fu-Jian Xu
The development of new materials for fast and sensitive protease assay is in demand for timely diagnosis of diseases, such as cardiovascular disease, cancers, and Alzheimer disease. Herein, poly(methacrylic acid) (PMAA) brushes were synthesized from the surfaces of silica nanoparticles via surface-initiated atom transfer radical polymerization (ATRP), and functionalized with series of proteolytically cleavable peptides for highly sensitive protease assay. Upon the proteolytic cleavage of the peptides, a short peptide fragment with fluorescent tag (GGK-FITC) is released to the solution, which can be easily detected with a benchtop fluorescence microscope. The grafting densities of PMAA brushes and peptides can be readily tuned by controlling the monomer concentrations of sodium methacrylate in the ATRP reaction. Because of the three-dimensional architecture of PMAA brushes, the loading amount of peptides can reach 21.4% of the total weight of functionalized silica particles (22.4 peptides/nm2), which is much higher than direct immobilization on silica nanoparticles without polymer brushes. Because of the high loading density of peptides, the limit of detection (LOD) of trypsin can reach 1.4 pM in buffer solution or 2.6 nM in nondiluted serum. By rational design of peptide substrates, the peptide-functionalized PMAA brushes can be readily expanded to detect other proteases, such as matrix metalloproteinase-2 (MMP-2), a virtual biomarker for many cancers, with an LOD of 1.1 pM. The proteolytically cleavable peptide-functionalized PMAA brushes offer a starting point for fast and sensitive protease assay.
研究领域:
材料科学
·
生物化学
·
纳米技术
·
生物医学工程
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Wang Zhiwei,Sun Lingshun,Wang Weixing,Wang Zheng,Shi Ge,Dai Honglian,Yu Aixi
Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix (ECM) and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsions (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit matrix metalloproteinases (MMPs), increase angiogenesis, and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties, and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition, and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis, and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance, and excellent mechanical properties.
研究领域:
材料科学
·
生物医学工程
·
药剂学
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE BIOLOGY
·
2016
·Vol. 249
·期 6
·757-767
·
IF 1.991
Lai Lu,Li Ya-Ping,Mei Ping,Chen Wu,Jiang Feng-Lei,Liu Yi
The mitochondrial toxicity induced by GSH-CdTe Quantum dots (QDs) of different sizes was investigated. The decreases in absorbance and transmission electron microscopy images show that QDs induce the swelling of mitochondria. Results of flow cytometry indicate that QDs cause a reduction of mitochondrial membrane potential (MMP). A remarkable increase in fluidity of protein regions of mitochondrial membrane is observed, whereas the lipid regions are not obviously affected. Cyclosporin A (CsA) effectively prevents the QD-induced mitochondrial swelling. On the basis of these results, it is proposed that QDs induce mitochondrial permeability transition (MPT). Moreover, with increasing QDs size, a pronounced MPT is observed. The difference between the membrane fluidity induced by QDs and Cadmium ion and the ineffective protective effects of EDTA suggests that the mitochondrial toxicity of QDs cannot be only attributed to the release of metal ion. The protective effects of HSA indicate that the interaction of QDs with pore-forming protein gives rise to the increase in membrane fluidity. This hypothesis is demonstrated by the interaction of QDs with model membranes and proteins using differential scanning calorimetry and isothermal titration microcalorimetry. In conclusion, as the size of QDs increases, the binding affinity of QDs with membrane protein increases, and therefore causes a pronounced mitochondrial damage.
研究领域:
纳米技术
·
毒理学
·
细胞生物学
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生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 45
·7141-7151
·
IF 5.047
Jun Zhang,Tiantian Zuo,Xiao Liang,Yingxin Xu,Yifan Yang,Tianxu Fang,Jing Li,Daijie Chen,Qi Shen
Triple-negative breast cancer (TNBC) is characterized by a high metastatic rate, which can seriously threaten women's health. ROS play an important role in tumor development and metastasis. Excessive ROS can induce tumor cell apoptosis and inhibit tumor cell metastasis. This study investigated Fenton-reaction-stimulative nanoparticles (P@P/H NPs) containing ROS-responsive molecular switches for antitumor metastasis by amplifying the ROS and activating the cascade biological reaction of ROS in tumor cells. Spheroidal P@P/H NPs exhibited a uniform size of 68.18 ± 0.29 nm, high drug cumulative release of 97.59% in response to H2O2 at 24 h, and satisfactory cytotoxicity with the IC50 value of 0.50 ± 0.02 μg mL−1. The markedly elevated ROS level caused by P@P/H NPs generated an evident antitumor metastasis effect in vitro by facilitating the expressions of cytochrome c, caspase-9, and caspase-3 and blocking that of matrix metalloprotein 9 (MMP-9). Moreover, P@P/H NPs engendered an excellent tumor inhibition rate of 56.37% and antitumor metastasis effect in vivo. Therefore, P@P/H NPs could respond to H2O2 in tumor cells to rapidly disassemble and further increase the ROS to induce antitumor metastasis via the Fenton reaction.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2024
·
IF 2.5
Gao Chong,Hu Zhong-He,Cui Zhen-Yu,Jiang Yu-Chen,Dou Jia-Yi,Li Zhao-Xu,Lian Li-Hua,Nan Ji-Xing,Wu Yan-Ling
Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl 4 ) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl 4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-β (TGF-β) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl 4 -induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1β, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl 4 -induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1β expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1β expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Waste and Biomass Valorization
·
2024
·
IF 2.6
Zhao Zijia,Gao Yan,Yuan Min,Ye Cai,Guo Yingxue,Zhao Yanli,Li Jinlian,Cui Jiwen,Dong Tianwei,Wu Dongmei
A significant quantity of residues will produce when volatile oil in Schisandra chinensis fruit is extracted by steam distillation. It is important to investigate the residues for potential use. Currently, there is an increasing demand for anti-photoaging products due to the skin damage caused by UV radiation. In this paper, the ingredients of the residues were investigated, and the anti-photoaging activities of residues extracts were studied. The results showed that the residues still contained notable amounts of lignans, flavonoids, and organic acids. In the extracted fraction of dichloromethane (DE), the residues contained higher amounts of schizandrol B and schisantherin A compared to the fresh fruit. The levels were particularly high at 17.39 ± 0.02 and 52.58 ± 0.04 mg/ml, respectively. By lowering the amount of matrix metalloproteinase-1 (MMP-1), reactive oxygen species (ROS) accumulation, and type I collagen (COL-I) loss in fibroblasts, the residues showed targeted benefits in the fight against skin photoaging. In particular, the DE-R phase of residues was very successful in raising the level of COL-I, matching or even exceeding that of retinol (ROL) and undistilled fresh fruits. Protocatechuic acid, schizandrol A, schizandrol B, schisantherinA, schisandrin A and schizandrin B were found to have a significant correlation with the anti-photoaging ability of residues. Particularly, there was a strong and significant correlation between an increase in COL-I and schizandrol B (|ρ| = 0.829*) and schisantherin A (|ρ| = 0.928**), and the distillation procedure has the potential to increase the amount of schizandrol B and schisantherin A in the residues. Graphical
研究领域:
药理学
·
化妆品科学
·
植物学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yinghuan Jing,Kangyu Wang,Tianxiang Pi,Zefan Chen,Tianhong Liu,Xinyu Liu,Hangyu Ye,Xinxing Xu,Yuanhui Zhao
Low molecular weight chondroitin sulfate (CS) has gained considerable attention for its superior bioactivity compared to native CS. In this study, the mechanisms of low molecular weight chondroitin sulfate from hybrid sturgeon cartilage (LMSCS), prepared using the H 2 O 2 /Vc system, on the remission of osteoarthritis (OA) were investigated both in in vitro and in vivo . A Caco-2/SW1353 co-culture cell model and a monosodium iodoacetate (MIA)-induced OA mouse model were used to validate its inhibited apoptosis, anti-inflammatory effects, and intestinal flora modulation. LMSCS was found to effectively alleviate inflammation, decrease chondrocyte apoptosis, and reduce MMP-13 levels by inhibiting the activation of NF-κB and MAPK signaling pathways. Notably, in vivo experiments, LMSCS exhibited significant anti-inflammatory effects compared to SCS. This trend, however, was not observed in vitro , which could be largely attributed to LMSCS' ability to regulate intestinal flora. Compared to SCS, LMSCS enhanced the abundance of beneficial bacteria, particularly, the Prevotellaceae_NK3B31_group and Akkermansia , and increased the levels of short-chain fatty acids such as butyrate and propionate. The effectiveness of LMSCS in mitigating inflammatory responses in vivo is thus largely due to its intestinal flora modulation, providing for its development and application.
研究领域:
药理学
·
风湿病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2017
·
IF 3.505
Jun Tian,Zhaoqun Lu,Yanzhen Wang,Man Zhang,Xueyan Wang,Xudong Tang,Xue Peng,Hong Zeng
The antifungal activity of Nerol (NEL) against Candida albicans , a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4 mM that causes noteworthy candidacidal activity through an apoptosis-like mechanism. Calcium (Ca 2+ ) levels and reactive oxygen species (ROS) production, which are the major causes of apoptosis, were determined in C. albicans cells treated with NEL and were found to increase, which related to mitochondrial dysfunction and disruption. A series of characteristic changes of apoptosis caused by NEL, including mitochondrial membrane depolarization, cytochrome c (cyt c) release, and metacaspase activation were examined using a flow cytometer and Western blot . The results showed that an increase in intracellular Ca 2+ and ROS led to dramatically decreased mitochondrial membrane potential (MMP); cyt c was also released from the mitochondria to the cytosol. Other early apoptotic features were also observed with the metacaspase activation. Finally, the morphological changes of the cells were observed, including phosphatidylserine (PS) externalization, nuclear condensation, and DNA fragmentation through Annexin V-FITC and PI double staining, TUNEL assay , and DAPI staining. The results supported the hypothesis that NEL was involved in the apoptosis of C. albicans cells not only at the early stages, but also at the late stages. In summary, NEL can trigger mitochondrial dysfunction and disruption via elevation of Ca 2+ and ROS leading to apoptosis in C. albicans . This research on the mechanism of cell death triggered by NEL against C. albicans has important significance for providing a novel treatment of C. albicans infections.
研究领域:
微生物学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）