SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
XiaoJing Zhang,ZhaoYi Miao,Yue Hu,XiaoTong Yang,YingYing Tang,Dong Zhu
Sensitive detection, especially in situ monitoring of intracellular MMP-2, is extremely desirable for cancer early diagnosis, evaluation of therapy, and discovery of the new anti-cancer drug. Herein, a programmed microcapsule-type MMP-2 responsive nanosensor based on mesoporous silica nanoparticles (MSN) is developed to realize in situ imaging monitoring of intracellular MMP-2. In the wrapping anti-MMP-2 antibody sealed microcapsule-type nanosensor, a black hole fluorescence quencher (BHQ-3) is covalently combined onto the inner walls of the MSN mesopores, and the fluorescein Cy5 is loaded in the cavity of MSN, resulting in fluorescence “OFF” state. With the existence of MMP-2, the anti-MMP-2 antibody which acts as a “bio-lid” could detach from the surface of the nanosensor owing to the binding MMP-2 with the antibody, leading to the release of the fluorescein Cy5 to produce fluorescence “ON” state. The prepared programmed microcapsule-type MMP-2 responsive nanosensor is capable of sensitive in situ imaging monitoring of intracellular MMP-2 and is further verified by tracking the change of intracellular MMP-2 level in response to MMP-2-repressive drugs. Thus, the nanosensor give a platform for in vivo detection of biomarkers for diagnosis, evaluation of therapy, and discovery of the new anti-cancer drug.
研究领域:
生物医学工程
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癌症研究
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纳米技术
·
药物发现
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Xiuting He,Zhongcheng Cao,Nuannuan Li,Liuxiang Chu,Jiazhen Wang,Chunyan Zhang,Xiaoyan He,Xiaoyan Lu,Kaoxiang Sun,Qingguo Meng
7-Ethyl-10-hydroxycamptothecin (SN-38)-loaded polyethylene glycol-GPLGVRG-poly β-benzyl- l -aspartic acid (PEG-GPLGVRG-PBLA) self-assemblies were successfully prepared using a classical nanoprecipitation method to give an enzyme-responsive nano-drug delivery system. The PEG-GPLGVRG-PBLA/SN-38 self-assemblies were characterized by transmission electron microscopy , dynamic light scattering , and high-performance liquid chromatography. The encapsulation efficiency was 91.7 ± 1.21% and the drug loading was 16.6 ± 0.93%. The 12 h in vitro release of SN-38 from PEG-GPLGVRG-PBLA/SN-38 treated with MMP-2 was 73.2 ± 2.05%, which was significantly higher than that for the group without MMP-2, demonstrating the enzyme-responsiveness of the nano-drug delivery system. In addition, the cellular uptake and tumor accumulation of PEG-GPLGVRG-PBLA were better than those of PEG-PBLA, and the blank PEG-GPLGVRG-PBLA showed high biocompatibility . These findings indicate that the enzyme-responsive nano SN-38 delivery system could provide new opportunities in tumor therapy.
研究领域:
药学
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生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Yuanxun Gong,Jiayi Zhang,Huiying Liang,Yanling Wang,Zichun Song,Jihua Wei,Qianli Tang,Kai Zhang,Xianjiu Liao
Matrix metalloproteinases (MMPs) are critical for the degradation of extracellular matrix components, which is essential for processes such as tissue remodeling, wound healing, and angiogenesis. MMP-2, in particular, degrades type IV collagen and is associated with diseases such as cancer and cardiovascular conditions, making it a significant biomarker. This study presents a novel electrochemical biosensor for the detection of MMP-2. The biosensor combines the specificity of a programmable RNA detection system with the amplification capabilities of T7 RNA polymerase and CRISPR/Cas12a. In the absence of MMP-2, Peptide Nucleic Acid (PNA) adsorbs on the DNA template, preventing RNA amplification and resulting in a low electrochemical signal. When MMP-2 is present, it cleaves a specific peptide, releasing the DNA template and enabling RNA synthesis. This activation leads to the cleavage of single-stranded DNA probes, increasing the electrochemical signal. The biosensor demonstrates high sensitivity with a detection limit of 0.496 fM for MMP-2 and excellent specificity, effectively distinguishing MMP-2 from other proteins. It successfully detected MMP-2 in biological samples, such as liver cancer cell supernatants, indicating its potential for clinical diagnostics. This innovative biosensor offers a powerful tool for the early detection and monitoring of diseases associated with MMP-2 activity.
研究领域:
生物医学工程
·
分子诊断
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2022
·
IF 9.221
Kai Zhang,Meina Yang,Helin Sun,Xueyin Wang,Hao Li,Jinxiang Han,Zhongwen Zhang
Using Peptide nucleic acid (PNA), this work provides a unique approach for controlling CRISPR/Cas13a activity by RNA Inhibitory PNA (RIP). This method reduces the action of CRISPR/Cas13a by inhibiting the binding of crRNA to CRISPR/Cas13a, which was subsequently utilized to detect metalloproteinase-2 (MMP-2) activity. We carefully constructed a PNA sequence that includes a peptide sequence (Gly-Pro-Leu-Gly-Val-Arg-Gly) that is particularly cleaved by MMP-2 in the middle. When MMP-2 is not present in the system, the PNA/crRNA complex reduces crRNA binding to CRISPR/Cas13a, hence inhibiting CRISPR/Cas13a cleavage activity. When MMP-2 is present in the system, it cleaves the peptide sequence (Gly-Pro-Leu-Gly-Val-Arg-Gly) selectively and so prevents PNA from binding to crRNA, enabling crRNA to reach the "free" form. Then, in the presence of an RNA activator, crRNA may bind to CRISPR/Cas13a and stimulate its activity. CRISPR/Cas13a triggered in this manner may precisely cleave the DNA sequence containing modified -UU- bases on the electrode surface . Thus, the ferrocene (Fc) is changed away from the electrode surface at one end of the DNA , enabling for the recovery of the Electrochemiluminescence (ECL) signal from the two-dimensional material transformed on the electrode surface. As a result, MMP-2 activity was detected utilizing this technique of inhibiting crRNA activity with a detection limit of 15.56 fM. Our suggested method of inhibiting CRISPR/Cas13a activity via PNA has a broad variety of potential therapeutic applications in gene editing and the development of CRISPR/Cas13a-based biosensors.
研究领域:
分子生物学
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基因编辑
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生物传感技术
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Ke Zhou,Yixin Zhu,Xuling Chen,Lingbing Li,Wei Xu
Tumor-responsive nanocarriers are highly valuable and demanded for smart anticancer drug delivery, where a quick release of chemotherapeutic drugs in tumors is preferred. Herein, a redox and MMP-2 sensitive nanoparticle has been designed for targeted delivery of PTX. Bovine serum albumin as a targeting ligand and gelatin as a hydrophilic carrier and MMP-2 sensitive reagent were used to construct the nanoparticles. Disulfide containing prodrug (PTX-SS-COOH) was grafted to the sulfhydryl modified gelatin to form the redox sensitive amphiphilic polymer. The nanoparticles were formed by self-assembly of amphiphilic polymer and BSA covering. Furthermore the modified sulfhydryl group on the gelatin can form a disulfide bond by self-crosslinking in the air, which endows the nanoparticle with a stable structure. The nanoparticle was sensitive to changes in MMP-2 concentration and redox potential, resulting in multiple responsive drug delivery to the tumor microenvironment. We further verified the anticancer effect of the nanoparticles both in vitro and in vivo , the nanoparticle (BSA/Gel-SS-PTX/PTX-SS-COOH NPs) demonstrated an excellent anticancer efficiency.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 12
·3397-3409
·
IF 5.831
Jing-Bo Hu,Di Liu,Jing Qi,Kong-jun Lu,Fei-yang Jin,Xiao-Ying Ying,Jian You,Yong-Zhong Du
Based on the overproduction of matrix metalloproteinase-2 (MMP-2) in renal tissue during acute kidney injury (AKI) occurrence, we developed a MMP-2 enzyme-triggered polymeric prodrug with sialic acid (SA) as the targeting group to the inflamed vascular endothelial cells for enhanced therapeutic outcomes. An MMP-2-responsive peptide, PVGLIG, was used to endow the polymeric prodrug with the ability to rapidly release the anti-inflammatory drug, curcumin (CUR), after the targeted site is reached and to improve the drug concentration in the target tissue. The sialic acid–dextran–PVGLIG–curcumin (SA-DEX-PVGLIG-CUR) polymeric prodrug was successfully synthesized via multi-step chemical reactions and characterized by 1H NMR. The water solubility of CUR was significantly increased in the polymeric prodrug and was approximately 23-fold higher than that of free CUR. The in vitro drug release results showed that the release rate of SA-DEX-PVGLIG-CUR was significantly enhanced compared to that of SA-DEX-CUR in a dissolving medium containing the MMP-2 enzyme, suggesting that SA-DEX-PVGLIG-CUR had rapid drug release characteristics in an inflammatory environment. A cellular uptake test confirmed that SA-DEX-PVGLIG-CUR was effectively internalized by inflamed vascular endothelial cells in comparison with that by normal cells, and the mechanism was associated with the specific interaction between SA and E-selectin receptors specifically expressed on inflamed vascular endothelial cells. Bio-distribution results further demonstrated the rapid and increased renal accumulation of SA-DEX-PVGLIG-CUR in AKI mice. Benefiting from the rapid drug release in renal tissue, SA-DEX-PVGLIG-CUR effectively ameliorated the pathological progression of AKI compared with free CUR and SA-DEX-CUR, as reflected by the improved renal functions, histopathological changes, pro-inflammatory cytokine production, oxidative stress and expression of apoptosis related proteins. Altogether, this study provided a new therapeutic strategy for the treatment of AKI.
研究领域:
药学
·
肾病学
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
World Journal of Acupuncture-Moxibustion
·
2025
·
IF 1.3
Xiao-lei ZHANG,Meng-ni HU,Ya-nan LI,Yao WANG,Zhen RONG,Jun MA
Objective
To investigate the effects of electroacupuncture (EA) on the blood-brain barrier permeability and the regulation of matrix metalloproteinases (MMPs) in the mice with Parkinson's disease (PD).
Methods
Forty-eight C57BL/6 mice were randomly assigned into the normal control (NC) group, the PD model (PD) group, the EA group and the EA + SB-3CT inhibitor group (EA + SB-3CT), with 12 mice in each group. In this experiment, the PD model was established by intragastric administration (IG) with rotenone for 4 wk in the PD group, EA group and EA+SB-3CT group. In the EA + SB-3CT group, 1 h after IG with rotenone, the mice were intraperitoneally injected with MMP-2/9 inhibitor, SB-3CT (25 mg/kg/d). After successfully modeled, in the EA group and EA + SB-3CT group, EA was conducted at “Fengfu (GV16)” and bilateral “Taichong (LR3)” and “Zusanli (ST36)”, at 1 mA and 2 Hz for 30 min each time, once a day, for consecutive 2 wk. The behavioral changes of the mice were observed in each group using the open field test, the level of tyrosine hydroxylase (TH) in the substantia nigra was determined by immunohistochemistry, the permeability of the blood-brain barrier was detected by Evans blue staining, and the protein expression of ZO-1, ocludin, claudin-1, MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting.
Results
Compared with the NC group, the behavioral scores increased (P < 0.05), while total time of locomotion, total distance and average speed were reduced (P < 0.05) in the PD group. The expression of TH in the substantia nigra decreased (P < 0.05), Evans blue level in the brain tissue increased (P < 0.05), and the protein expression of ZO-1, occludin and claudin-1 was lower (P < 0.05), whereas MMP-2 and MMP-9 expression was higher (P < 0.05) in the PD group. Compared with the PD group, behavioral scores decreased (P < 0.05), while the total time of locomotion, total distance and average speed increased (P < 0.05) in the EA group. Additionally, TH expression in the substantia nigra was elevated (P < 0.05), Evans blue level in the brain tissue was lower (P < 0.05), the protein expression of ZO-1, occludin and claudin-1 was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was down-regulated (P < 0.05) in the EA group. Compared with the EA group, Evans blue level was reduced (P < 0.05), the protein expression of ZO-1 and occludin was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was further down-regulated (P < 0.05) in the EA+SB-3CT group.
Conclusion
EA can effectively ameliorate the motor dysfunction of PD mice, reduce the damage of dopaminergic neurons, and play a neuroprotective role. EA can effectively improve the blood–brain barrier permeability in PD mice by up-regulating the expression of tight junction proteins, ZO-1 and occludin, and down-regulating the expression of matrix metalloporteinases, MMP-2 and MMP-9. The neuroprotective role of EA may be obtained by improving the blood-brain barrier permeability mediated by MMP-2/9 pathway.
研究领域:
神经科学
·
药理学
·
病理生理学
·
中医
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Tianjiao Ji,Suping Li,Yinlong Zhang,Jiayan Lang,Yanping Ding,Xiao Zhao,Ruifang Zhao,Yiye Li,Jian Shi,Jihui Hao,Ying Zhao,Guangjun Nie
Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy.
研究领域:
癌症生物学
·
药学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Hao Wu,Xuefeng Ding,Yun Chen,Yanfei Cai,Zhaoqi Yang,Jian Jin
Antibody–drug conjugates (ADC) are an inevitable trend in the development of modern “precision medicine”. The goal of this work is to produce enzyme-responsive antibody nanoparticle-loaded medication (FMSN-Dox-H2-AE01) based on the EGFR antibody (AE01) and human serum albumin (HSA) shelled mesoporous silica nanoparticles. HSA and antibodies on the surface of the particlescan not only enhance the biocompatibility of the particle and avoid early drug leakage but also allow selective biodegradation triggered by matrix metalloproteinase-2 (MMP-2), which are overexpressed enzymes in some tumor tissues. The cytotoxicity test confirmed favorable safety and efficacy of the ADC. The mortality rate of cancer cells is about 85–90%. Moreover, the antibody nanoparticle-loaded drug showed distinguishing controlled release efficiency toward cancer cells induced by different levels of MMP-2 and pH. This enzyme-responsive FMSN-Dox-H2-AE01 offers a promising option for cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Qiang Chen,Chunjing Guo,Huimin Guo,Yanguo Su,Zhongxin Liu,Min Cao,Daquan Chen
With the improvement of people’s living standards, obesity has become a health threat, but an effective drug treatment for obesity has not been found yet. Here, we suggest the use of celastrol, a pentacyclic triterpenoid from the traditional Chinese medicine Tripterygium wilfordii, which has a powerful antiobesity effect. Increasing studies have discovered that obesity is closely related to inflammation. In addition, MMP-2 enzyme is highly expressed in inflammatory sites. According to the principle of the prodrug, celastrol was used as a hydrophobic group, PVGLIG as a link, and dextran sulfate as a hydrophilic group to form a micelle (DS-PVGLIG-Cel). Celastrol was then loaded for the effective treatment of high-fat-diet (HFD)-induced obesity. MMP-2-sensitive assays confirmed that PVGLIG cleavage by MMP-2 enzymes favors the synchronous release of celastrol. A series of animal experiments tested that the preparation group has a strong weight loss effect. Our results suggest that this will shed light on a strategy for the subsequent effective treatment of HFD obesity.
研究领域:
药学
·
生物医学工程
·
代谢疾病研究
✓ 已验证
DOI
高影响因子
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
·
2020
·
IF 2.802
Qiyu Liu,Zhe Yang,Ning Ma,Weixing Wang,Yangqun Li
This study aimed to investigate the long-term scar hypertrophy in the rabbit transplanted oral mucosa and scrotal skin with changed matrix environment, as well as the scar location expression, quantitative analysis of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and biomechanical changes in the transplanted tissues. The split-thickness skin grafts were collected from the oral mucosas and scrotal skins of 30 male rabbits, and prepared into reelpipes for autologous transplantation into the rabbit back muscular tissues. Samples were collected to carry out elastic tensile mechanical detection and histological observation. The maximum longitudinal tensile displacement of scrotal skin before 8 weeks of transplantation was greater than that after 8 weeks of transplantation (P < 0.05). The expression intensities of MMP-2 and TIMP-2 in the oral mucosa and in scrotal skin at 2 W time point were higher than those at T o time point (P < 0.05). The expression quantities of TIMP-2 in oral mucosa and scrotal skin during 8–24 W were higher than those of MMP-2 (P < 0.05). At 8 W time point, the TIMP-2/MMP-2 ratio in scrotal skin was higher than that in oral mucosa (P < 0.05). MMP-2 and TIMP-2 expression in normal oral mucosa and scrotal skin is weak, but their expression is remarkably up-regulated after 2 weeks of transplantation, revealing that scar formation was related to the high expression of MMP-2 and TIMP-2. At the 8th–24th weeks, the AOD values of TIMP-2 in oral mucosa and scrotal skin are apparently higher than those of MMP-2; moreover, the TIMP-2/MMP-2 ratio in scrotal skin at the 8th week was higher than that in oral mucosa, which can well explain the earlier scar formation in scrotal skin than in oral mucosa, and it also suggests that the different expression levels between TIMP-2 and MMP-2 may account for the important cause of scar formation.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Yiwen You,Zhiyuan Xu,Yun Chen
HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH2 (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDYCDGFYACYMDV-NH2, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX via a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as in vitro model systems and nude mice with BT474 xenografts as an in vivo model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower in vitro IC50, and its in vivo extent of inhibition in mice was more evident. During this process, enzymatic cleavage of MAHNP-DOX is critical for its activation and cellular uptake. In addition, a synergistic response was observed after the combination of DOX and AHNP. This effect was probably due to the involvement of AHNP in the PI3K–AKT signaling pathway, which can be largely activated by DOX and leads to anti-apoptotic signals.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 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）