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
·
基因编辑
·
生物传感技术
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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
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 11
·1932-1940
·
IF 4.872
Jing-Jing Hu,Li-Han Liu,Ze-Yong Li,Ren-Xi Zhuo,Xian-Zheng Zhang
In this paper, we report on an intelligent mesoporous silica-based multifunctional theranostic nanoplatform (designated as MMTNP) for tumor imaging as well as controlled drug release. This theranostic nanoplatform consists of MCM-41 typical mesoporous silica nanoparticles (MSNs) as a hydrophobic drug carrier, matrix metalloprotease-2 (MMP-2) activated fluorescence imaging peptides on the surface of MSNs served as diagnostic probes as well as enzyme-responsive nanovalves blocking the pores, and cRGD peptides further functionalized on the surface of MSNs for tumor targeting. In the absence of MMP-2 conditions, the proximity between the fluorescent dye 5(6)-carboxytetramethylrhodamine hydrochloride (TAMRA) and the quencher 4,4-dimethylamino-azobenzene-4′-carboxylic acid (Dabcyl) on the surface of MSNs resulted in no fluorescence. When the drug loaded nanoplatform arrived at tumor tissue with overexpressed MMP-2, the fluorescence of TAMRA became recovered efficiently due to the hydrolysis of the MMP-2 sensitive peptide substrate, realizing tumor imaging and triggering drug release. In addition, the further introduced cRGD peptide significantly enhanced the targeting efficiency through receptor-mediated endocytosis in tumor cells.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2022
·Vol. 148
·期 4
·752-761
·
IF 5.227
Xintong Lu,Luoyu Ding,Haohan Song,Wenxin Yu,Chaoqing Dong,Jicun Ren
Matrix metalloproteinase-9 (MMP-9) plays an important role in tumor progression. It is of great significance to establish a sensitive in situ assay strategy for MMP-9 activity in single living cells. Here a novel in situ single molecule spectroscopy method based on the fluorescence correlation spectroscopy (FCS) technique was proposed for measuring the MMP-9 activity at different locations within single living cells, using a fluorescent specific peptide and a reference dye as dual probes. The measurement principle is based on the decrease of the ratiometric translational diffusion time of dual probes in the detection volume due to the peptide cleavage caused by MMP-9. The peptide probe was designed to be composed of an MMP-9 cleavage and cell-penetrating peptide sequence that was labeled with a fluorophore and conjugated with a streptavidin (SAV) molecule. The ratiometric translational diffusion time was used as the measurement parameter to eliminate the effect of intracellular uncertain viscosity. The linear relationship between the ratiometric diffusion time and MMP-9 activity was established, and applied to the determination of enzymatic activity in cell lysates as well as the evaluation of the inhibitory effects of different inhibitors on MMP-9. More importantly, the method was successfully used to dynamically determine MMP-9 activity in single living cells or under the stimulation with phorbol 12-myristate 13-acetate (PMA) and inhibitors.
研究领域:
生物化学
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分子生物学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 54
·31264-31273
·
IF 3.049
Wei Li,Cheng Tao,Jiexin Wang,Yuan Le,Jianjun Zhang
The complex construction within the oral cavity causes incomplete surgical resection of oral squamous cell carcinoma (OSCC) that may enhance the risk of recurrence and metastasis in the treatment. In situ forming injectable hydrogels with minimally invasive procedures, encapsulation stability and stimuli-responsive degradation have emerged as promising carriers for local drug delivery. In this study, doxorubicin (DOX) was first encapsulated in biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA) micelles and then loaded into an in situ injectable hyaluronic acid (HA) hydrogel, which was cross-linked by a matrix metalloproteinase-2 (MMP-2)-responsive peptide (GCRDGPQGIWGQDRCG) through a Michael addition reaction. In vitro studies demonstrated that the HA hydrogel had a sensitive MMP-2-responsive drug release profile. Investigations including MTT, live-dead, apoptosis, and wound healing assays illustrated that DOX micelle-loaded HA hydrogels exhibited outstanding cytotoxicity against squamous carcinoma cells (SCC-15). Furthermore, by in vivo studies, we also proved that HA hydrogels degraded faster in the tumor site than in normal tissue, which led to a local sustained release of DOX-loaded micelles and tumor growth inhibition of oral squamous cell carcinoma (OSCC) without any damage to the organs. Therefore, this work provides a remarkable drug delivery platform for local chemotherapy and other applications.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Zhina Wu,Yingtong Wang,Yaqin Zhang,Jingzheng Yi,Yutong Li,Jiasi Wang,Min Hu,Di Wang
Periodontitis is one of the most prevalent oral diseases, and the diagnosis and monitoring of periodontitis rely on clinical and imaging examinations. Matrix metalloproteinase-8 (MMP-8) in saliva is a reliable indicator of periodontitis. The traditional detection method is enzyme-linked immunosorbent assay (ELISA), which requires professional expertise and is not sensitive enough to low-abundance protein detection. In this study, we developed a nanoimmunoassay combined with clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated protein (Cas)12a for ultrasensitive detection of MMP-8 in saliva. Antibody-DNA-gold nanoparticles (AuNPs) and trans-cleavage activity of CRISPR/Cas12a were employed for signal amplification. With this protocol, the limit of detection (LoD) for MMP-8 was reduced to the fg/mL, indicating 100-fold higher sensitivity than that of the commercial ELISA kit and its amenability for ultrasensitive detection of trace proteins. The diagnostic sensitivity of the assay was 100 %, and the specificity was 83.3 % based on the testing of 23 clinical saliva samples. The sensitivity and specificity were considerably higher than those for ELISA. Thus, this immuno-CRISPR/Cas12a assay holds promise for both diagnosing and monitoring periodontitis in clinical settings.
研究领域:
口腔科学
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分子生物学
·
生物技术
·
临床诊断
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产品关联
DOI
高影响因子
JOURNAL OF FOOD PROCESSING AND PRESERVATION
·
2020
·Vol. 44
·期 4
·e14383
·
IF 1.405
Zi-qiang Liu,Da-yong Zhou,Yu-xin Liu,Xiao-yang Liu,Yan Liu,Bing Liu,Liang Song,Fereidoon Shahidi
Matrix metalloprotease (MMP) is the key endogenous protease that boosts the autolysis of sea cucumber, while its action and mechanism in vivo are still unclear. MMP inhibitor (1,10-phenanthroline) was injected into coelomic cavity of sea cucumber ( Stichopus japonicus ) and its effects on autolysis and mechanism of action were investigated for the first time by using scanning electron microscopy, multi-functional in vivo imaging system, and confocal laser scanning microscopy. In response to external stimuli, the level of Ca 2+ in live sea cucumber dermis increased, which may activate MMP activity. MMP inhibitor could diffuse from coelomic cavity into body wall and significantly prevented the activation of MMP by chelating Ca 2+ , and thus, retarded the autolysis of fresh sea cucumber by preventing degradation of interfibrillar proteoglycan bridges between adjacent collagen fibrils. This work provides information toward understanding the mechanism behind the sea cucumber autolysis and demonstrate a potential approach to prevent the autolysis. Practical applications Autolysis occurs in sea cucumber in response to external stimulation. Matrix metalloproteinase (MMP) has been found to be the key endogenous protease that boosts the autolysis of sea cucumber body wall (SCBW). However, the role of MMP in the autolysis of SCBW in vivo and the mechanisms involved remain unclear. In this study, MMP inhibitor (1,10-phenanthroline) was injected into the body cavity of live sea cucumber, and its effects on in situ changes in SCBW were studied. Our results indicated that the activity of endogenous MMP in live SCBW was activated in response to external stimulation, which may be responsible for the autolysis. After injection into coelomic cavity, MMP inhibitor could diffuse into SCBW and significantly reduced the progress of typical morphological and microstructural changes of autolytic sea cucumber. Through chelating Ca 2+ , the MMP inhibitor could prevent the activation of MMP, and thus reduced the autolysis of fresh sea cucumber.
研究领域:
海洋生物学
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生物化学
·
蛋白质组学
·
水产养殖
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Hao Meng,Jianlong Su,Qi Shen,Wenzhi Hu,Pinxue Li,Kailu Guo,Xi Liu,Kui Ma,Weicheng Zhong,Shengqiu Chen,Liqian Ma,Yaying Hao,Junli Chen,Yufeng Jiang,Linlin Li,Xiaobing Fu,Cuiping Zhang
Chronic diabetic wounds are characterized by prolonged inflammation and excessive accumulation of M1 macrophages, which impede the healing process. Therefore, resolving inflammation promptly and transitioning to the proliferative phase are critical steps for effective diabetic wound healing. Exosomes have emerged as a promising therapeutic strategy. In this study, a smart hydrogel capable of responding to pathological cues in the inflammatory microenvironment to promote the transition from inflammation to proliferation by delivering M2 macrophage-derived exosomes (M2-Exos) is developed. The smart hydrogel is synthesized through the cross–linking of oxidized dextran, a matrix metalloproteinase (MMP)-9-sensitive peptide, and carboxymethyl chitosan containing M2-Exos. In response to elevated MMP-9 concentrations in the inflammatory microenvironment, the hydrogel demonstrates diagnostic logic, adjusting the release kinetics of M2-Exos accordingly. The on-demand release of M2-Exos facilitated macrophage polarization from the M1 to the M2 phenotype, thereby promoting the transition from the inflammatory to the proliferative phase and accelerating diabetic wound healing. The transcriptomic analysis further reveals that the MMP-9-responsive hydrogel with M2-Exos delivery exerts anti-inflammatory and regenerative effects by downregulating inflammation-related pathways. This study introduces an innovative, microenvironment-responsive exosome delivery system that enables precise control of therapeutic agent release, offering a personalized approach for the treatment of chronic diabetic wounds.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Xiaoyan Zhou,Qianqian Zheng,Changyong Wang,Jiake Xu,Jian-Ping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.
研究领域:
药物学
·
癌症研究
·
聚合物化学
·
基因治疗
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Shijia Lu,Chenxiao Zhang,Huiru Wu,Junjie Wang,Jinglong Wang,Limei Zhao,Tianyang Ren,Guofei Li
Liver cancer is one of the malignant tumors with high morbidity and mortality worldwide and lacks effective clinical treatments. CD8 + T cell-based immunotherapy is the most promising option for the treatment of liver cancer, but its application is severely limited by low infiltration and functional exhaustion of CD8 + T cells in liver cancer tissues. To overcome this problem, in this study, pH/matrix metalloproteinase-9 (MMP-9) dual-responsive liposomes were constructed and co-loaded with a galectin-3 (Gal-3) inhibitor, GB1107, a programmed death receptor 1 (PD-1) inhibitor, BMS1166, and an androgen receptor (AR) antagonist, enzalutamide, for immunotherapy studies in liver cancer. Specifically, the co-loaded liposomes (GBE@LP) were produced with a one-two punch targeting antitumor immunity. First, GBE@LP exhibited prolonged circulation in the blood and accumulated in liver cancer tissues through the enhanced permeability and retention effect due to the presence of surface polyethylene glycol. After entering liver cancer tissues, GBE@LP responded to the low pH and overexpression of MMP-9 in the microenvironment to promote the release of GB1107, BMS1166, and enzalutamide, thus, realizing the intelligent release of drugs targeting liver cancer. Upon reaching liver tumor tissues, GB1107 can inhibit overexpressed Gal-3 to transform liver cancer from a “cold” to a “hot” tumor and enable deep penetration by CD8 + T cells. In addition, BMS1166 and enzalutamide inhibit PD-1 and AR in CD8 + T cells, reversing CD8 + T cell exhaustion and enhancing their killing activity. In vivo and in vitro experiments confirmed the significant antitumor effects of GBE@LP in liver cancer. These results indicate that our strategy is expected to reverse the “cold” tumor and immune exhaustion state of liver cancer, which not only improves therapeutic efficacy, but also provides a new paradigm for the exploration of liver cancer immunotherapy.
研究领域:
肿瘤学
·
药理学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2021
·Vol. 33
·期 11
·115702
·
IF 3.874
Dan Zhu,Anran Li,Yunsong Di,Zhuyuan Wang,Jingzhan Shi,Xiaoqi Ni,Yiping Wang
The expression of membrane type-1 matrix metalloproteinase (MT1-MMP) in cancer cells is critical for understanding the development, invasion and metastasis of cancers. In this study, we devised an interference-free surface-enhanced Raman scattering (SERS) nanoprobe with high selectivity and specificity for MT1-MMP. The nanoprobe was comprised of silver core-silica shell nanoparticle with a Raman reporter tag (4-mercaptobenzonitrile) embedded in the interface. Moreover, the nitrile group in 4-mercaptobenzonitrile shows a unique characteristic peak in the Raman-silent region (1800–2800 cm−1), which eliminates spectral overlapping or background interference in the Raman fingerprint region (500–1800 cm−1). After surface modification with a targeting peptide, the nanoprobe allowed visualization and evaluation of MT1-MMP in breast cancer cells via SERS spectrometry. This interference-free, peptide-functionalized SERS nanoprobe is supposed to be conducive to early diagnosis and invasive assessment of cancer in clinical settings.
研究领域:
生物医学工程
·
癌症生物学
·
纳米技术
·
分子成像
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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
危险品化学品经营许可证（带存储）