Molecular Medicine Reports
·
2017
·Vol. 16
·期 2
·1383-1388
·
IF 1.692
Tao Liu,Xidong Wu,Yigang Wang,Xiongjun Hou,Gang Jiang,Ting Wu,Huifen Xie,Minqiang Xie
The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized star‑shaped co‑polymer consisting of β‑cyclodextrin (CD) and a poly(L‑lysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP‑9) small interfering RNA, via CD‑PLLD/DOC/MMP‑9 complexes, into mice implanted with HNE‑1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic co‑polymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CD‑PLLD/DOC/MMP‑9 inhibited HNE‑1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP‑9 was investigated; CD‑PLLD/DOC/MMP‑9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the blood‑brain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE‑1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.
研究领域:
肿瘤学
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药学
·
分子生物学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Xu Lu,Ming Li,Keqiang Bo,Bin Zheng,Xu Hun
A photoelectrochemical (PEC) assay strategy for the detection of matrix metalloproteinase-9 (MMP-9) was fabricated. RuSe 2 /CuO nanohybrids were first prepared by hydrothermal method. As a transition metal element semiconductor, RuSe 2 has excellent optical and electrical properties. By combining the excellent conductivity and adjustable bandgap of CuO, a binary heterojunction nanoflower with high photoelectric response was obtained. The combination of RuSe 2 and CuO reduces the electron hole recombination rate; the RuSe 2 /CuO nanohybrids exhibits a higher photocurrent response. In the MMP-9 PEC strategy determination, the magnetic beads (MB)-peptide-alkaline phosphatase (ALP) recognition probe was formed by modifying C-terminal of the peptide chain with biotin and binding to ALP, and the N-terminal was connected to carboxylated MB. When the target MMP-9 exists, the recognition probe, MB-Peptide-ALP, was recognized by MMP-9 to cut the substrate area and coding area and release ALP, catalyzing the hydrolysis of O-phosphonoxyphenol (OPP) to produce benzene-1,2-diol in situ, the photocurrent response was generated. This strategy provides lower background PEC noise for detecting MMP-9, with the advantage of simplicity and the sensitivity than conventional ELISA. The results showed that the recognition peptide probe PEC method achieved ultra-high sensitivity detection of target MMP-9, with a linear detection range of 1 pg/mL–100 ng/mL and a detection limit of 0.3 pg/mL (S/N = 3). The results of PEC assay strategy in human serum sample give the recoveries rate of 94.3 % to 108.1 % and relative standard deviation of 0.45–5.87 %.
研究领域:
纳米技术
·
生物化学
·
分析化学
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医学诊断
✓ 已验证
产品关联
DOI
高影响因子
Brain Sciences
·
2022
·Vol. 12
·期 5
·571
·
IF 3.333
Chao Song,Chao Gao,Zhenxin Wang
(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been investigated. (2) Method: Adult male mice received 2.3 mg/kg cisplatin or saline injections for three cycles consisting of five daily injections followed by 5 days of rest. Procyanidin or saline was administered 1 h prior to cisplatin treatment. Cognitive testing, gelatin zymography, and blood–brain-barrier (BBB) penetration tests were performed after treatment cessation. RAW264.7 cells were treated by stimulated supernatant of SHSY5Y cells. In addition, high-mobility group protein B1 (HMGB1) expression and MMP-9 activity were tested. (3) Results: Repeated cisplatin treatment increased BBB penetration, MMP-9 activity, impaired performance in contextual fear conditioning, and novel object recognition tasks. The knockout of MMP-9 rescues cognitive impairment and cisplatin-induced upregulation of HMGB1 in SHSY5Y cells. HMGB1/TLR4/IP3K/AKT signaling contributes to the increased MMP-9 activity in RAW264.7 cells. Procyanidin treatment attenuates MMP-9 activity, BBB damage, and CICI. (4) Conclusions: The results indicated that MMP-9 activation and BBB disruption is involved in CICI. Procyanidin may effectively alleviate the harmful effects of cisplatin.Keywords:cisplatin;chemotherapy;MMP-9;RAW264.7 cells;procyanidin;blood–brain barrier (BBB);chemotherapy-induced cognitive impairment (CICI)
研究领域:
肿瘤学
·
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Xuejiao Zhang,Jiaxin Gu,Congying Zhao,Yaozhong Hu,Bowei Zhang,Jin Wang,Huan Lv,Xuemeng Ji,Shuo Wang
Non-nutritive sweeteners are the most widely used food additives designed to provide sweetness and reduce caloric intake. Studies have confirmed a link between sweeteners and colitis, yet supporting scientific data remain exiguous and controversial. In this study, three common sweeteners (Saccharin sodium, Stevioside, and Sucralose) in acceptable daily intake dosage were added to water in order to determine their effects on dextran sodium sulfate-induced colitis in mice. Our results show that the three sweeteners meliorate colitis to varying degrees─Saccharin exerts the most pronounced effect, followed by Stevioside and Sucralose. Intake of sweeteners alleviates colitis symptoms, alters gut microbiota, reshapes the TH17/Treg balance, protects the intestinal barrier, and reduces inflammation. Most significantly, sweeteners can enhance the abundance of Mucispirillum and Alistipes, which are conducive to colitis recovery, and upregulate the expression of E-cadherin through the miR-15b/RECK/MMP-9 axis to improve intestinal barrier integrity. Moreover, by inhibiting the MMP-9/AKT/NF-κB pathway, inflammation is relieved, as reflected in the restoration of the Th17/Treg balance. Our results link the consumption of sweeteners to the remission of colitis, which provides new scientific evidence for the safe use of sweeteners.
研究领域:
药理学
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免疫学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2016
·
IF 6.008
Qianming Lin,Yumeng Yang,Qian Hu,Zhong Guo,Tao Liu,Jiake Xu,Jianping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly( l -lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with α-cyclodextrin (α-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by α-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on α-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system , this supramolecular hydrogel is a promising candidate for long-term gene therapy. Statement of Significance To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between α-cyclodextrin and PEGylated arginine-functionalized poly( l -lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering.
研究领域:
生物材料学
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基因治疗
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Na Li,Liqun Yang,Chenglin Pan,Phei Er Saw,Meng Ren,Biyun Lan,Junfeng Wu,Xiaoyi Wang,Tingting Zeng,Liyan Zhou,Li-Ming Zhang,Chuan Yang,Li Yan
s The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro , while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. Statement of significance In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.
研究领域:
生物医学工程
·
药剂学
·
伤口愈合
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糖尿病
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2019
·
IF 10.159
Siming Yu,Rong Wen,Haiyang Wang,Yongchao Zha,Lin Qiu,Bo Li,Wei Xue,Dong Ma
Au nanoclusters (Au NCs) are materials that hold great promise in biomedical applications due to their improved photophysical properties. However, the current nonthiolate polymer-based self-assembly methods for preparing Au NCs face drawbacks of usage of environmentally unfriendly reducing reagents or nonbiocompatible polymers, which largely hamper their more extensive biomedical use. In this work, biocompatible chitosan-graft-poly(l-lysine) (CPL) dendrons are designed and synthesized based on a simple azide–alkyne cyclization reaction for facile preparation of Au@CPL NCs in one step. The obtained Au@CPL NCs exhibited enhanced computer tomography imaging property as compared with clinically used iohexol (Omnipaque) and displayed high delivery efficiency for matrix metalloproteinase-9 plasmid shRNA (pMMP-9). After surface functionalization by cyclic arginine-glycine-aspartic (Arg-Gly-Asp, RGD), a peptide that specifically targets αvβ3 integrin overexpressed by cancer cells, the resultant Au@CPL-RGD/pMMP-9 complex can precisely and efficiently inhibit tumor growth both in vitro and in vivo. Our work provides a novel strategy to fabricate Au NCs with enhanced biorelevant properties for more efficient cancer diagnosis and therapy.
研究领域:
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR NEUROBIOLOGY
·
2023
·Vol. 60
·期 7
·3824-3838
·
IF 5.1
Deng Ling,Zhang Jiyu,Chen Sha,Wu Yu,Fan Xiaomei,Zuo Tianrui,Hu Qingwen,Jiang Lu,Yang Shaonan,Dong Zhi
Blood-brain barrier (BBB) disruption can induce further hemorrhagic transformation in ischemic stroke (IS). miR-671-5p, a micro-RNA, is abundant in the cortex of mammalian brains. Herein, we investigated the roles and potential mechanisms for the effects of miR-671-5p on BBB permeability in IS. Results showed that miR-671-5p levels were significantly downregulated in the cerebral cortex of middle cerebral artery occlusion/reperfusion (MCAO/R) C57/BL6 mice in vivo . miR-671-5p agomir administration via right intracerebroventricular injection significantly reduced infarct volume, improved neurological deficits, the axon of neurons and nerve fiber, attenuated cell injury and apoptosis, as well as reduced BBB permeability in MCAO/R mice. Treatment with miR-671-5p agomir alleviated tight junction proteins degradation, including claudin, occludin, and ZO-1 in MCAO/R mice, and these effects were reversed following NF-κB overexpression. Bend.3 brain endothelial cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) treatment in vivo , and then miR-671-5p agomir was transfected into the cells. This resulted in reduction of cytotoxicity, improved cell viability, trans-endothelial electrical resistance, reduced fluorescein sodium permeability, and inhibited tight junction degradation in Bend.3 OGD/R cells. However, these effects were reversed following NF-κB overexpression. These results demonstrated that upregulation of miR-671-5p in IS models in vivo and i n vitro alleviated BBB permeability by targeting NF-κB/MMP-9. In summary, miR-671-5p is a potential therapeutic target for protecting BBB permeability in IS to minimize cerebral hemorrhage transformation.
研究领域:
神经科学
·
分子生物学
·
药理学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR IMMUNOLOGY
·
2024
·
IF 3.7
Jingying Qin,Cheli Wang,Xiaoying Zhou
Reduced glutathione (GSH) is an antioxidant involved in redox homeostasis, and recently regarded as an inducer of Reductive stress. Its immune-regulatory effects on lymphocytes have not been extensively studied. This study is based on the finding that much increased GSH level in collagen-induced arthritis (CIA) rat spleen, and aimed to investigate the effects of GSH (0, 1, 10, 100 mM) on normal and immune-stimulated spleen lymphocytes respectively. The elevated GSH level is associated with the increased levels of inflammatory factors; especially the increased DPP1 activity indicated immune-granulocytes activation in CIA rat spleen. Exogenous GSH had different influences on normal and CIA lymphocytes, affecting intracellular levels of GSH, Glutathione-S-transferases (GSTs) and Reactive oxygen species (ROS); as well as the expressions of NF-κB, MMP-9, Bcl-2, GST, P38, PCNA and TLR4. The increased extracellular GSH level disturbed redox homeostasis and induces reductive stress to spleen lymphocytes, which decreased intracellular GSH concentration and influenced the MAPK/PCNA and NF-κB/MMP-9 signaling pathways, as well as cell cycles respectively, leading to cell senescence/ferroptosis/apoptosis. This study also revealed the multiple faces of GSH in regulating spleen lymphocytes, which depended on its levels in tissue or in cells, and the activation status of lymphocytes. These findings indicate the immune-regulatory role of GSH on spleen-lymphocytes, and the high level GSH in CIA rat spleens may contribute to CIA development.
研究领域:
免疫学
·
药理学
·
细胞生物学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yanan Kang,Lu Lu,Jinshuai Lan,Yue Ding,Jing Yang,Yong Zhang,Yuan Zhao,Tong Zhang,Rodney J.Y. Ho
A novel redox-sensitive system for co-delivering hydrophobic drugs and hydrophilic siRNA or shRNA was developed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs) through amide bonds, which is called GA-conjugated PAAs (PAG). PAG can self-assemble into micelles as amphiphilic block copolymers , which exhibits an excellent loading ability for the co-delivery of docetaxel (DTX) and MMP-9 shRNA with adjustable dosing ratios. In addition, confocal microscopy , flow cytometry and in vitro transfection analyses demonstrated more efficient cellular internalization of DTX and MMP-9 shRNA after incubation with PAG/DTX- MMP-9 shRNA micelles (PAG/DTX-shRNA) than with free drugs. Unlike traditional amphiphilic copolymer micelles, GA conjugated in PAG possesses an intrinsic anticancer efficacy. The presence of disulfide bonds in PAAs enables rapid disassembly of PAG micelles in response to reducing agents, inducing the release of loaded drugs (DTX, GA and MMP-9 shRNA). In vitro cellular assays revealed that PAG/DTX-shRNA micelles inhibited MCF-7 cell proliferation more efficiently than the single drug or single drug-loaded micelles. In vivo biodistribution and anti-tumor effect studies using an MCF-7 breast cancer xenograft mouse model have indicated that PAG/DTX-shRNA micelles can enhance drug accumulation compared with the free drug, thereby sustaining the therapeutic effect on tumors. Additionally, PAG/DTX-shRNA micelles displayed a greater anti-tumor efficacy than Taxotere® and PAG-shRNA micelles. These results suggest that the redox-sensitive PAG platform is a promising co-delivery system for combining drugs and gene therapy for the treatment of cancer. Statement of Significance The PAG micelles were designed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs), which would serve dual purposes as both gene and drugs co-delivery carrier and an anti-tumor prodrug. Unlike traditional amphiphilic micelles, GA conjugated in PAG could exert its intrinsic efficacy and provide synergistic antiproliferative effects with docetaxel (DTX) on MCF-7 cells. Disulfide bonds in PAG enables a rapid disassembly of PAG micelles in response to reducing agents and to release all loaded drugs (DTX, GA and MMP-9 shRNA) at tumor sites. PAG/DTX-shRNA micelles displayed greater anti-tumor efficacy than that of Taxotere®, indicating the design concept for PAG works well. And the strategy for PAG could be used to develop a series of similar co-delivery systems through conjugations of other small-molecule drugs with PAAs, such as doxorubicin , methotrexate and other drugs with carboxy groups in their structure.
研究领域:
药学
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纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Jing Li,Jun Zhang,Yiyue Wang,Xiao Liang,Zaitongguli Wusiman,Yunzhi Yin,Qi Shen
Metastasis impedes the successful chemotherapy for breast cancer. In this study, an Akt inhibitor (quercetin, Qu) was co-delivered with a chemotherapeutic agent (docetaxel, DTX) by using hyaluronic acid (HA)-modified nanoparticles (NPs) as vectors to block metastasis. Dual DTX/Qu-loaded HA/polylactic-co-glycolic acid–polyethyleneimine NPs (PP-HA/NPs) were prepared through a modified emulsion solvent evaporation technique. The particle size of PP-HA/NPs with narrow polydispersity was 209.8 ± 10.8 nm. Wound healing assay revealed that Qu co-delivery and HA modification elicited synergistic inhibitory effects on cell motility. The downregulation of p-Akt and matrix metalloproteinase-9 (MMP-9) expression contributed to the significant inhibition of cell migration and invasion with inhibition rates of 95.6% and 99.3%, respectively. Further studies indicated that PP-HA/NPs could be efficiently uptaken by 4T1 breast cancer cells and could further induce cytotoxicity, decrease colony formation and promote cell apoptosis. Biodistribution assay demonstrated PP-HA/NPs also enhanced drug accumulation in the tumor and lungs and predicted that PP-HA/NPs could be employed as an effective therapy for primary tumor and pulmonary metastasis . Therefore, PP-HA/NPs could be a promising delivery system to treat metastatic breast cancer effectively.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
细胞生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Wanyi Zhou,Zhiguang Duan,Jing Zhao,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/ [email protected] &INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib ( [email protected] ). Temperature-sensitive self-adaptive CBP/ [email protected] &INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/ [email protected] &INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/ [email protected] &INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.
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
危险品化学品经营许可证（带存储）