ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jieqiong Chen,Qing Zhao,Jiajing Tang,Xiaoyu Lei,Jinzheng Zhang,Yuping Li,Jidong Li,Yubao Li,Yi Zuo
Inspired by the crucial role of matrix vesicles (MVs), a series of biomimetic vesicles (BVs) fabricated by calcium glycerophosphate (CaGP) modified polyurethane were designed to mediate the mineralization through in situ enzyme activation for bone therapy. In this study, alkaline phosphatase (ALP) was harbored in the porous BVs by adsorption (Ad-BVs) or entrapment (En-BVs). High encapsulation of ALP on En-BVs was effectively self-activating by calcium ions of CaGP-modified PU that specifically hydrolyzed the organophosphorus (CaGP) to inorganic phosphate, thus promoting the formation of the highly oriented bone-like apatite in vitro. Enzyme-catalyzed kinetics confirms the regulation of apatite crystallization by the synergistic action of self-activated ALP and the confined microcompartments of BVs. This leads to a supersaturated microenvironment, with the En-BVs group exhibiting inorganic phosphate (Pi) levels 4.19 times higher and Ca2+ levels 3.67 times higher than those of simulated body fluid (SBF). Of note, the En-BVs group exhibited excellent osteo-inducing differentiation of BMSCs in vitro and the highest maturity with reduced bone loss in rat femoral defect in vivo. This innovative strategy of biomimetic vesicles is expected to provide valuable insights into the enzyme-activated field of bone therapy.
研究领域:
生物材料学
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骨再生医学
·
组织工程
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DOI
PubMed
高影响因子
Chemical Science
·
2024
·Vol. 15
·期 23
·8922-8933
·
IF 7.6
Hao-Hua Deng,Kai-Yuan Huang,Yu Zhong,Ye Li,Hong-Xiang Huang,Xiang-Yu Fang,Wei-Ming Sun,Qiaofeng Yao,Wei Chen,Jianping Xie
Surface-protecting ligands, as a major component of metal nanoclusters (MNCs), can dominate molecular characteristics, performance behaviors, and biological properties of MNCs, which brings diversity and flexibility to the nanoclusters and largely promotes their applications in optics, electricity, magnetism, catalysis, biology, and other fields. We report herein the design of a new kind of water-soluble luminescent gold nanoclusters (AuNCs) for enzyme-activatable charge transfer (CT) based on the ligand engineering of AuNCs with 6-mercaptopurine ribonucleoside (MPR). This elaborately designed cluster, Au5(MPR)2, can form a stable intramolecular CT state after light excitation, and exhibits long-lived color-tunable phosphorescence. After the cleavage by purine nucleoside phosphorylase (PNP), the CT triplet state can be easily directed to a low-lying energy level, leading to a bathochromic shift of the emission band accompanied by weaker and shorter-lived luminescence. Remarkably, these ligand-engineered AuNCs show high affinity towards PNP as well as decent performance for analyzing and visualizing enzyme activity and related drugs. The work of this paper provides a good example for diversifying physicochemical properties and application scenarios of MNCs by rational ligand engineering, which will facilitate future interest and new strategies to precisely engineer solution-based nanocluster materials.
研究领域:
材料科学
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生物化学
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纳米医学
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DOI
PubMed
高影响因子
CELLULAR MICROBIOLOGY
·
2018
·Vol. 20
·期 6
·e12827
·
IF 4.41
Lian Xu,Zhi-Zhen Pan,Jing Zhang,Li-Yang Niu,Jie Li,Zheng Chen,Bo Liu,Yu-Jing Zhu,Qing-Xi Chen
Cry2Ab, a pore-forming toxin derived from Bacillus thuringiensis , is widely used as a bio-insecticide to control lepidopteran pests around the world. A previous study revealed that proteolytic activation of Cry2Ab by Plutella xylostella midgut juice was essential for its insecticidal activity against P. xylostella , although the exact molecular mechanism remained unknown. Here, we demonstrated for the first time that proteolysis of Cry2Ab uncovered an active region (the helices α4 and α5 in Domain I), which was required for the mode of action of Cry2Ab. Either the masking or the removal of helices α4 and α5 mediated the pesticidal activity of Cry2Ab. The exposure of helices α4 and α5 did not facilitate the binding of Cry2Ab to P. xylostella midgut receptors but did induce Cry2Ab monomer to aggregate and assemble a 250-kDa prepore oligomer. Site-directed mutagenesis assay was performed to generate Cry2Ab mutants site directed on the helices α4 and α5, and bioassays suggested that some Cry2Ab variants that could not form oligomers had significantly lowered their toxicities against P. xylostella . Taken together, our data highlight the importance of helices α4 and α5 in the mode of action of Cry2Ab and could lead to more detailed studies on the insecticidal activity of Cry2Ab.
研究领域:
昆虫学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Mengxin Zhang,Yingyu Zhang,Xianwei Zhang,Qionglin Wang,Kangbo Liu,Muchun Yu,Lifeng Li,Zhidan Yu,Huan Zhao,Weyland Cheng,Wancun Zhang
Specific imaging of tumor cells with high sensitivity is urgently needed for evaluating the risk of tumor metastasis and progression. However, traditional tumor cell imaging strategies are still restricted by limited tumor specificity and sensitivity due to off-tumor signal leakage and a lower content of the targets. Therefore, a self-powered and self-recycled strategy based on molecular beacon (MB) hybridized on tetrahedral framework DNA (E-MB-tFNA) using the endogenous enzyme, apurinic/apyrimidinic endonuclease 1 (APE1), was rationally developed for tumor cell-specific molecular imaging with superior spatial specificity and improved sensitivity. The apurinic/apyrimidinic site (AP site) can be specifically recognized and cleaved by APE1, and was modified on the stem and loop region of E-MB-tFNA. The resultant E-MB-tFNA can be specifically recognized and cleaved by APE1 in the cytoplasm, which is overexpressed in tumor cells compared to normal cells. In particular, once APE1 cleaves the AP site on the stem region (double-stranded DNA) of E-MB-tFNA, the self-powered and self-recycled sequences modified on the stem region of E-MB-tFNA is freed to hybridize with the loop region of E-MB-tFNA, prompting APE1 to further hydrolyze the E-MB-tFNA loop region and generate fluorescence signals. In addition, the self-powered and self-recycled sequences can be hybridized with other E-MB-tFNA to continuously and cyclically amplify the fluorescence signal. The experimental results of this study showed that the E-MB-tFNA has the capability to monitor drug resistance and achieve guided precision surgical excision in vivo with superior spatial specificity and improved sensitivity. In particular, E-MB-tFNA can realize the risk classification of neuroblastoma patients in clinical plasma.
研究领域:
生物医学工程
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分子生物学
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肿瘤学
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DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 29
·6001-6012
·
IF 4.726
Sen Lin,Fangfang Deng,Ping Huang,Lingli Li,Lei Wang,Qing Li,Ling Chen,Hao Chen,Kaihui Nan
Legumain is the only acidic asparaginly-endopeptidase in mammals that is highly up-regulated in tumor tissue and tumor associated cells. In this study, a novel legumain protease-activated micelle was successfully synthesized and prepared by loading with doxorubicin (DOX). The prepared micelle exhibited a spherical morphology and possessed a low critical micelle concentration of 1.21 × 10−3 mg mL−1 with a DOX loading capacity and entrapment efficiency of 4.05% and 60.6% respectively. The release profile of DOX from this micelle formulation was observed to be legumain concentration dependent. The micelle encapsulation of DOX highly enhanced the cellular uptake of DOX by tumor cell lines of DAOY, Y79, MCF-7, and MCF-7/DOX. Furthermore, encapsulation of DOX boosts the cytotoxicity against the tumor cells while reducing cytotoxicity against RPE and HEK293 cells. In addition, blank micelles did not exhibit any biological effects on tumor or RPE or HEK293 cells at the concentration range of 0–300 μg mL−1, indicating good biocompatibility. The results suggest that this micelle formulation has potential applications in sustained drug delivery for legumain up-regulated tumors.
研究领域:
药学
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 145
·期 10
·3626-3633
·
IF 3.978
Julan Xia,Sujuan Sun,Xianhua Wu,Yan Huang,Chunyang Lei,Zhou Nie
In a cellular microenvironment, numerous biomolecules are involved in various physiological and pathological processes. However, for the in-depth and comprehensive understanding of their roles at the molecular level, there is still a lack of detection techniques for the in situ tracking of these biomolecules in a local environment. Herein, we engineered a membrane insertion peptide (MIP) as an enzyme-activated membrane insertion peptide probe (eaMIP) that allowed the in situ tracking of the activity of target enzymes in living cells. In this strategy, the membrane insertion capacity of the MIP motif in each eaMIP was caged by appending a chemical moiety. In the presence of target enzymes, the caging moiety in each eaMIP was removed by enzymatic decaging, leading to the generation of active MIPs. The versatility of this design was demonstrated by lighting up different tumor cells with distinct fluorescence signal patterns, affording an alternative tool for clinical diagnostics, biochemical research and membrane engineering.
研究领域:
细胞生物学
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生物技术
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癌症研究
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分子生物学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 6
·期 17
·2547-2556
·
IF 4.543
Zelin Chen,Bowen Li,Xin Xie,Fang Zeng,Shuizhu Wu
DT-diaphorase is a cytosolic flavoenzyme whose level is strongly elevated in a number of tumor types. Incorporating a DT-diaphorase's substrate in the structure of anticancer drugs may facilitate cancer detection and therapy. Herein, we developed a novel pro-prodrug nanosystem for cancer detection and therapy, which features enzyme-activated fluorescence emission and subsequent light-triggered drug release. The pro-prodrug molecule comprises an anticancer drug methotrexate (MTX), an enzyme (DT-diaphorase) responsive quinone propionic acid moiety and a light-activatable coumarinyl. In the absence of DT-diaphorase, the quinone propionic acid moiety quenches the fluorescence of coumarin via photoinduced electron transfer (PET) and blocks the photocleavage pathway. DT-diaphorase can annihilate the effect of PET and restore the fluorescence of coumarin. This fluorescence serves as the reporting signal for assessing the enzyme biomarker level and discriminates tumor cells from normal cells, and subsequently photocontrollable release of the active drug, MTX, can be activated via one- or two-photon irradiation. This pro-prodrug nanosystem shows strong cytotoxicity toward cancer cells and a negligible effect on normal cells. This strategy provides a new platform for constructing nanosystems for cancer detection and subsequent on-demand selective killing of cancer cells via both internal- and external-stimuli activation.
研究领域:
药理学
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肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 2
·344
·
IF 3.267
Limin Qu,Ke Song,Qi Zhang,Jie Guo,Juan Huang
Tyrosinase inhibitors with excellent inhibitory activities and lower side effects have promising applications in the fields of medicine, agriculture, food sciences and cosmetics. In this study, a method for simultaneous separation and determination of six target compounds (puerarin, daidzin, genistein, daidzein, genistin, and formononetin) inPuerariae LobataeRadix was established by cloud point extraction (CPE) and concentration combined with high performance liquid chromatography (HPLC). To achieve high extraction yields, an ultrasound-assisted extraction method was developed based on a salt-modified Triton X-100 system. The optimal extraction conditions are: surfactant Triton X-100 concentration 0.07 g/mL, liquid-solid ratio 80:1 (mL/g), NaCl addition amount 0.6 g, equilibrium time 40 min, equilibrium temperature 70 °C. Under the optimal conditions, the total maximum extraction yield of the six target isoflavones reached 8.92 mg/g. Usingl-tyrosine andl-dopa as substrates, the effects of puerarin on the monophenolase and diphenolase activity of tyrosinase activity were investigated by the enzyme kinetics method. The results showed that puerarin inhibited monophenolase activity with an IC50of 0.537 mg/mL and activated diphenolase activity. The inhibition type of puerarin on monophenolase and the activation type of puerarin on diphenolase were analyzed by Lineweaver-Burk plots which show that puerarin showed mixed inhibition on monophenolase and mixed activation on diphenolase. Therefore, puerarin can be used as both a tyrosinase inhibitor and a tyrosinase activator.Keywords:Puerariae LobataeRadix;cloud point extractions;tyrosinase inhibitors;tyrosinase activator;kinetic analysis
研究领域:
药理学
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植物化学
·
酶学
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DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 12
·6231-6241
·
IF 2.936
Wenqian Nong,Anran Zhao,Jinrui Wei,Hui Cheng,Xuan Luo,Cuiwu Lin
A series of benzothiazole amide derivatives were synthesized through a facile and efficient method via a nucleophilic acyl substitution reaction between 2-aminobenzothiazole and various cinnamic acid compounds. The obtained products exhibited good thermal stabilities. All compounds were evaluated for their in vitro hemostatic activities using the commercially available standard drug etamsylate as a positive control. The results showed that compound Q2 had a significant partial coagulation activity, reduced capillary permeability at 5, 10 and 50 μmol L−1, activated thrombin activity, and a more potent platelet aggregation activity than the positive control group (etamsylate, up to 1283.9 times in the nanomole range). A molecular modeling study revealed that compound Q2 was a competitive thrombin activator. Therefore, Q2 may be a potential lead for further biological screening and for the generation of drug molecules. Moreover, the structure–activity relationship of the prepared compounds is also discussed herein.
研究领域:
药物化学
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药理学
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止血研究
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Shi-Ying Li,Hong Cheng,Wen-Xiu Qiu,Li-Han Liu,Si Chen,Ying Hu,Bo-Ru Xie,Bin Li,Xian-Zheng Zhang
In this paper, we aimed to develop a conjugate of matrix metalloproteinases-2 (MMP-2)-sensitive activable cell-penetrating peptide (R9GPLGLAGE8, ACPP) with protoporphyrin (PpIX) for tumor-targeting photodynamic therapy. In normal tissue, the cell-penetrating function of polycationic CPP (R9) would be blocked by a polyanionic peptide (E8) through intramolecular electrostatic attraction. Once exposed to MMP-2 existing at the tumor site, proteolysis of the oligopeptide linker (GPLGLAG) between the CPP and the polyanionic peptide would dissociate the inhibitory polyanions and release CPP-PpIX for photodynamic therapy (PDT). It was found that after tail vein injection the ACPP-PpIX conjugate could accumulate effectively at the tumor site with the fluorescence enhancement which was beneficial for tumor diagnosis and image-guided PDT. After further administration with irradiation, both the solid tumor size and weight had a significant suppression (reduced by more than 90%) with a low systemic toxicity. This ACPP-PpIX conjugate delivery system activated by MMP-2 would be a promising strategy for tumor-targeted treatment.
研究领域:
癌症研究
·
药学科学
·
分子生物学
·
治疗学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2023
·
IF 5.9
Shengkai Luo,Yi Hou,Song-Qing Hu
Although the oxidation of tea polyphenols catalyzed by polyphenol oxidases (PPOs) is an attractive method for the synthesis of theaflavins (TFs), PPOs for synthesizing TFs were impure, and either not activated or activated by classical chemical methods. Herein, high pure PPO from Rosa chinensis (RcPPO) was cleanly and efficiently activated, and the MBP-RcPPO zymogen was successfully expressed in E. coli BL21 (DE3) with a high pure yield of 37.20 mg/L. Enzymatic activity of the RcPPO after proteolytic activation with trypsin in vitro increased to 5.52 times compared with the MBP-RcPPO zymogen, obtaining a 1625.00 U/L yield of activated enzyme with a specific activity of 480.77 U/mg for 25 mmol/L catechol, and could be enhanced by CuSO 4 , MgCl 2 , DMSO and ethanol. The MBP-RcPPO zymogen was specifically cleaved at the peptide bond of R (−5)-I (−4) for N-terminal, but not specifically cleaved at multiple cleavage sites for C-terminal during the activation with trypsin. RcPPO has been classified as tyrosinase with the obvious preference for diphenol compound substrates. Moreover, the four major TFs were synthesized from tea polyphenols extract by RcPPO with a higher efficiency than native PPO from Camellia sinensis , and the yield of TFs monomers could be furtherly improved using the corresponding purified tea polyphenols as substrate. The results indicated that activated RcPPO may serve as a promising biocatalyst for commercial-scale production of TFs.
研究领域:
生物化学
·
分子生物学
·
生物技术
·
食品科学
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产品关联
DOI
高影响因子
Nano Research
·
2018
·Vol. 11
·期 7
·3762-3770
·
IF 7.994
Sun Panpan,Zhang Yan,Ran Xiang,Liu Chaoying,Wang Zhenzhen,Ren Jinsong,Qu Xiaogang
Though phytochemicals are a promising alternative to traditional antibiotics for combating resistant bacteria, the low water solubility and lack of selectivity seriously hinder their widespread applications. Herein, we constructed a hyaluronidase-activated “on-demand” delivery nanocarrier to encapsulate plant essential oils (PEOs) for the synergistic treatment of multidrug-resistant bacteria. The bioavailability and selectivity of PEOs was enhanced and the antibacterial effect was significantly improved by combining with the photothermal effect of the nanocarrier. This antibacterial system was successfully applied for healing methicillin-resistant Staphylococcus aureus -infected wound with negligible cytotoxicity and biotoxicity in mice. Given the increasing risk of antibiotic resistance, we believe that this phytochemical-encapsulated nanoplatform would provide a long-term solution and be a new powerful tool for skin-associated bacterial infections.
研究领域:
药理学
·
纳米技术
·
微生物学
·
材料科学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）