ULTRASONICS SONOCHEMISTRY
·
2015
·
IF 4.321
Zhi-Long Yu,Wei-Cai Zeng,Wen-Hua Zhang,Xue-Pin Liao,Bi Shi
Gelatin is a mixture of soluble proteins prepared by partial hydrolysis of native collagen. Gelatin can be enzymatically hydrolyzed to produce bioactive hydrolysates. However, the preparation of gelatin peptide with expected activity is usually a time-consuming process. The production efficiency of gelatin hydrolysates needs to be improved. In present work, effect of ultrasonic pretreatment on kinetic parameters of gelatin hydrolysis by collagenase was investigated based on an established kinetic model. With ultrasonic pretreatment, reaction rate constant and enzyme inactivation constant were increased by 27.5% and 27.8%, respectively. Meanwhile, hydrolysis activation energy and enzyme inactivation energy were reduced by 36.3% and 43.0%, respectively. In order to explore its possible mechanism, influence of sonication on structural properties of gelatin was determined using atomic force microscopy, particle size analyzer, fluorescence spectroscopy, protein solubility test and Fourier transform infrared spectroscopy. Moreover, hydrogen peroxide was used as a positive control for potential sonochemical effect. It was found that reduction of gelatin particle size was mainly caused by physical effect of ultrasound. Increased solubility and variation in β-sheet and random coil elements of gelatin were due to sonochemical effect. Both physical and chemical effects of sonication contributed to the change in α-helix and β-turn structures. The current results suggest that ultrasound can be potentially applied to stimulate the production efficiency of gelatin peptides, mainly due to its effects on modification of protein structures.
研究领域:
食品科学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 5
·1-12
·
IF 4
Liu Xiaoqing,Dong Xiaoling,Peng Zhen,Wang Cuihong,Wan Jianwei,Chen Min,Zheng Chunli
In this study, a quercetin-loaded liposome system modified with collagenase was developed to increase QU penetration in the ECM and improve IPF treatment. Quercetin-loaded long circulation liposome (QU-LP) and quercetin-loaded liposome modified with collagenase type I (QU-CLP) were prepared, followed by characterization of the encapsulation efficiency, particle size, morphology, and in vitro drug release. Their effect on the cytotoxicity of A549 cells was detected by the Cell Counting Kit-8, and the cellular uptake was investigated using cellular fluorescence imaging and flow cytometry. TGF-β1 induced A549 cell model was established to mimic pulmonary fibrosis to explore further the anti-pulmonary fibrosis effect of QU-CLP by CCK8 experiment. QU-CLP significantly improves the solubility and bioavailability of QU by encapsulating it in the internal cavity with a high encapsulation efficiency (EE%) of 92.86 ± 1.03%. Liposomes alleviate the influence of QU on normal A549 cell growth. Enhanced fluorescence intensity was observed in A549 cells treated with coumarin 6-labeled and collagenase-modified nanoliposomes (C6-CLP) after 4 h of incubation on the collagen matrix, confirming that collagenase-loaded liposomes could penetrate the collagen barrier and cells internalized more hydrophobic drug. The mean fluorescence intensity (MFI) of the C6-CLP group was 2.88 times that of the C6-labeled nanoliposomes (C6-LP). Moreover, QU-CLP significantly (** P < 0.01) inhibited the proliferation of A549 cells stimulated by TGF-β1. QU-CLP has excellent potential for delivering QU with enhanced bioavailability, high cellular uptake efficiency, and improved therapeutic efficacy in IPF. Graphical abstract
研究领域:
药剂学
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生物医学工程
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
·
2022
·Vol. 147
·期 16
·8757-8764
·
IF 4.755
Ma Tong,Sun Wendell Q.,Wang Jian
Biological scaffolds are increasingly used for tissue repair and regeneration. In order to provide critical data for rational design of tissue matrix products, the present study evaluated thermophysical stability and biodegradability of seven commercially available bio-scaffold products that have been approved for clinical implantation by Chinese and US Regulatory Authorities. Calorimetrical analysis shows that the onset denaturation temperature (T d ) of these scaffolds in the dry state (equilibrated to the same water activity ( a w ) of 0.75) varies from 89.7 to 106.9 °C, but T d decreases to 36.2 ~ 59.5 °C upon rehydration, suggesting that some of these products might be unstable at body temperature. The incubation study at 37 °C indicates that T d of tissue matrix needs to be > 43 °C for implantation. T d of tissue matrices tested in the dry state is correlated poorly to T d measured after rehydration in physiological saline, demonstrating that the design of biological scaffolds should consider the role of water in stability of supramolecular assemblies. T d of hydrated tissue matrices is highly correlated with degradation rate by collagenase, while no such correlation exists between T d measured in the dry state and collagenase degradation. This study has discovered that calorimetrical analysis is a valuable analytical tool, not only for thermophysical stability of regenerative tissue matrices, but also for the rapidly-indirect evaluation of their biodegradability.
研究领域:
生物医学工程
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材料科学
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再生医学
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DOI
高影响因子
Nature Nanotechnology
·
2025
·
IF 34.9
Zhao Zhipeng,Li Qian,Qu Chenghao,Jiang Zeyu,Jia Guoqing,Lan Gongde,Luan Yuxia
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of haematological malignancies. Challenges in overcoming physical barriers however greatly limit CAR-T cell efficacy in solid tumours. Here we show that an approach based on collagenase nanogel generally improves the outcome of T cell-based therapies, and specifically of CAR-T cell therapy. The nanogels are created by cross-linking collagenase and subsequently modifying them with a CXCR4 antagonist peptide. These nanogels can bind CAR-T cells via receptor–ligand interaction, resulting in cellular backpack delivery systems. The nanogel backpacks modulate tumoural infiltration and localization of CAR-T cells by surmounting physical barriers and disrupting chemokine-mediated CAR-T cell imprisonment, thereby addressing their navigation deficiency within solid tumours. Our approach offers a promising strategy for pancreatic cancer therapy and holds potential for advancing CAR-T cell therapy towards clinical applications.
研究领域:
肿瘤学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Shuifang Mao,Xiaoli Liu,Wenshui Xia
In this study, chitosan oligosaccharide (COS) was modified by grafting Linalool (Lin) on its backbone to improve its anti-inflammatory activity. By changing the molar ratios of COS to Lin, three different degrees of substitution COS-g-Lin1-3 were prepared. The degrees of substitution of derivatives were 0.65, 0.80 and 1.14 respectively. The structure of COS-g-Lin1-3 were characterized by UV–vis, FT-IR, 1 H NMR and elemental analysis in order to show the COS-g-Lin1-3 successfully synthesized. Besides, the thermal stability , solubility, pH stability as well as crystallinity were also investigated. The results revealed that the derivatives exhibited higher thermal stability and more remarkable anti-inflammatory property against hyaluronidase and collagenase than that of COS. The good biocompatibility made this novel material a promising and effective compound for anti-inflammatory applications.
研究领域:
药学
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材料科学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 46
·5880-5885
·
IF 2.378
Jiexia Chen,Guang-Chao Zhao,Yan Wei,Dexiang Feng
A signal-on photoelectrochemical (PEC) biosensing platform was developed here for the highly sensitive detection of a cancer marker type IV collagenase, which relied on the exciton energy transfer (EET) between CdTe quantum dots (QDs) and Ag nanoparticles (NPs) combined with the catalytic hydrolysis of a protease. A special sequence peptide chain with positively charged arginines at one end and a cysteine-labeled terminal at the other end, which could be modified with Ag NPs, was designed and synthesized. CdTe QDs and synthetic peptide were assembled onto the surface of indium–tin oxide (ITO) electrodes by means of a layer-by-layer self-assembly technology. The as-obtained modified electrodes generated a lower photocurrent under irradiation due to the effect of EET. The photocurrent intensity increased due to the addition of type IV collagenase, which could specifically hydrolytically cleave Gly–Pro–Ala, leading to Ag NPs being away from the electrode surface. Thus, a signal-on PEC biosensor could be obtained. Under optimum conditions, the PEC biosensor for type IV collagenase exhibited a linear range from 0.5 to 50 μg mL−1 and sensitivity of 96 ng mL−1. The peptide-QD-based PEC detection against type IV collagenase showed a promising potential for other protease or kinase detection when we changed the substrate of the peptide.
研究领域:
生物医学工程
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分析化学
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癌症诊断
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产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Jingwen Luo,Zhiwei Zhang,Yingchun Zeng,Yanming Dong,Lixin Ma
Components of the extracellular matrix (ECM) are overexpressed in fibrotic liver. Collagen is the main component of the liver fibrosis stroma. Here we demonstrate that chondroitin sulfate coated multilayered 50-nm nanoparticles encapsulating collagenase and silibinin (COL + SLB-MLPs) break down the dense collagen stroma, while silibinin inhibits activated hepatic stellate cells. The nanoparticles were taken up to a much greater extent by hepatic stellate cells than by normal hepatocytes, and they down-regulated production of type I collagen. In addition, chondroitin sulfate protected the collagenase from premature deactivation. COL + SLB-MLPs were delivered to the cirrhotic liver, and the collagenase and silibinin synergistically inhibited fibrosis in mice. Immunofluorescence staining of liver tissues revealed that CD44, mediated by chondroitin sulfate, delivered the nanoparticles to hepatic stellate cells. This strategy holds promise for degrading extracellular stroma and thereby facilitating drug penetration into fibrotic liver and related diseases such as liver cirrhosis and liver cancer.
研究领域:
药学
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生物医学工程
·
肝脏疾病研究
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Bowen Duan,Hongting Liu,Xiaoxuan Ji,Jingwen Dong,Xinping Luo,Feiran Zhang,Minjie Sun,Zhanwei Zhou
Osteosarcoma is one of the commonest malignant bone tumors in children and adolescents, and its preferred treatment is chemotherapy. However, the lack of sufficient blood vessels in the bone tissue and the dense collagen fibers in osteosarcoma severely weaken the drug-directional accumulation effect and intra-tumoral penetration, leading to poor therapeutic efficacy. Herein, we reported a bone-targeted permeable nanomicelle (Co1-PTX@DSAA) composed of aspartic acid (Asp)-modified dextran (DSAA) to deliver paclitaxel (PTX) and collagenase 1 (Co1) simultaneously for highly effective osteosarcoma treatment. The prepared nanomicelle possessed excellent osteosarcoma targeting ability as Asp can combine with hydroxyapatite (HAP) in bone. More intelligently, the surface-absorbed Co1 endowed PTX@DSAA with a special function like a nano-icebreaker, which could quickly destroy the collagen fibers to promote PTX penetration deeply in the tumor. Our work suggests that Co1-PTX@DSAA nanomicelles could quickly combine with HAP and Ca 2+ at an adsorption rate of ∼ 60% and ∼ 32%, respectively. Meanwhile, the penetration depth of Co1-PTX@DSAA could even reach 70 μm in the multicellular spheroids (MCSs) model. The tumor treatment efficiency of Co1-PTX@DSAA is 1.51 times that of free PTX. Overall, this unprecedented nanomicelle can simultaneously facilitate drug accumulation and deep penetration in the tumor, which will provide a promising strategy for future safe and high-efficiency clinical osteosarcoma treatment.
研究领域:
肿瘤学
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药学
·
纳米技术
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产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Chen Zhiyong,Wei Yingxian,Liang Likun,Wang Xu,Peng Fangfei,Liang Yiying,Huang Xin,Yan Kaiqi,Gao Yunxia,Li Kangjing,Huang Xiaoman,Jiang Xinglu,Chen Wenxia
Objectives: To study the ability of theaflavin-3,3’-digallate (TF3)/ethanol solution to crosslink demineralized dentin collagen, resist collagenase digestion, and explore the potential mechanism.Methods: Fully demineralized dentin blocks were prepared using human third molars that were caries-free. Then, these blocks were randomly allocated into 14 separate groups (n = 6), namely, control, ethanol, 5% glutaraldehyde (GA), 12.5, 25, 50, and 100 mg/ml TF3/ethanol solution groups. Each group was further divided into two subgroups based on crosslinking time: 30 and 60 s. The efficacy and mechanism of TF3’s interaction with dentin type I collagen were predicted through molecular docking. The cross-linking, anti-enzymatic degradation, and biomechanical properties were studied by weight loss, hydroxyproline release, scanning/transmission electron microscopy (SEM/TEM), in situ zymography, surface hardness, thermogravimetric analysis, and swelling ratio. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy were utilized to explore its mechanisms. Statistical analysis was performed using one and two-way analysis of variance and Tukey’s test.Results: TF3/ethanol solution could effectively crosslink demineralized dentin collagen and improve its resistance to collagenase digestion and biomechanical properties (p < 0.05), showing concentration and time dependence. The effect of 25 and 50 mg/ml TF3/ethanol solution was similar to that of 5% GA, whereas the 100 mg/mL TF3/ethanol solution exhibited better performance (p < 0.05). TF3 and dentin type I collagen are mainly cross-linked by hydrogen bonds, and there may be covalent and hydrophobic interactions.Conclusion: TF3 has the capability to efficiently cross-link demineralized dentin collagen, enhancing its resistance to collagenase enzymatic hydrolysis and biomechanical properties within clinically acceptable timeframes (30 s/60 s). Additionally, it exhibits promise in enhancing the longevity of dentin adhesion.
研究领域:
牙科材料
·
胶原化学
·
生物力学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Bowen Deng,Rui Huang,Rui Liang,Yang Fei,Qing Luo,Guanbin Song
Altered tissue mechanics is vital for cancer development and malignancy, whether targeting the mechanical microenvironment could retard the initiation and progression of tumor is less explored. In this study, an orthotopic hepatocellular carcinoma (HCC) rat model was constructed to reproduce the mechanical and pathophysiological microenvironment of HCC development. LpMSN@CLG, a liver-targeted (L) and pH-sensitive (p) mesoporous silica nanoparticle (MSN) encapsulated with collagenase type-I (CLG), and DOX-LpMSN@CLG, on the basis of LpMSN@CLG, encapsulated with CLG and doxorubicin (DOX), were prepared to reduce matrix stiffness by degrading collagen in liver and HCC tumor. LpMSN@CLG, and DOX-LpMSN@CLG were respectively injected (i.v.) into rats at the stage of fibrosis and HCC, resulting in decreased collagen content in liver and HCC tissue, as well as reduced matrix stiffness. In addition, LpMSN@CLG treatment at the fibrosis stage retarded HCC initiation, and DOX-LpMSN@CLG treatment inhibited the growth of HCC tumor when compared with that of the rats treated by DOX alone, suggesting that reducing matrix stiffness in HCC tumor can improve the therapeutic efficacy of DOX. Taken together, our study demonstrated that mechanical intervention of tissue stiffness by CLG-loaded nanoparticles could retard the initiation and progression of HCC, suggesting the promising of mechanical intervention of hepatocellular carcinoma.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-16
·
IF 10.2
Li Juanjuan,Gong Chunai,Chen Xinlu,Guo Huanhuan,Tai Zongguang,Ding Nan,Gao Shen,Gao Yuan
Background Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability.Methods We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study.Results Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox.Conclusion sThis multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.
研究领域:
药理学
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纳米技术
·
癌症研究
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Liyue Zhou,Qiangwei Liang,Yifan Li,Yongjing Cao,Juan Li,Jiayu Yang,Jinxia Liu,Jiawei Bi,Yanhua Liu
Liver fibrosis is a pathological process of multiple chronic liver diseases progressing to cirrhosis for which there are currently no effective treatment options. During fibrosis progression, the overproduction of extracellular matrix (ECM) collagen secreted by hepatic stellate cells (HSCs) greatly impedes drug delivery and reduces drug therapeutic effects. In this study, a glycyrrhetinic acid (GA)-conjugated prodrug micellar system with collagenase I (COL) decoration (COL-HA-GA, abbreviated as CHG) was designed to codelivery sorafenib (Sora/CHG, abbreviated as S/CHG) for potentiating ECM degradation and HSCs targeting on liver fibrosis therapy. In ECM barrier models established in vitro or in vivo , CHG micelles efficiently degraded pericellular collagen and demonstrated enormous ECM penetration abilities as well as superior HSCs internalization . Moreover, CHG micelles exhibited more Sora & GA accumulations and activated HSCs targeting efficiencies in the fibrotic livers than those in the normal livers. More importantly, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating the fibrosis-related factors, leading to reverse the fibrotic liver to normal liver through the multi-mechanisms including angiogenesis reduction, liver fibrosis microenvironment regulation, and epithelial-mesenchymal transition inhibition. In conclusion, the developed COL decorated nano-codelivery system with fibrotic ECM collagen degradation and activated HSCs targeting dual-functions exhibited great potential for liver fibrosis therapy. Statement of significance A glycyrrhetinic acid (GA)-conjugated prodrug with collagenase I (COL) decoration (CHG) was designed for codelivery with sorafenib (S/CHG), potentiating extracellular matrix (ECM) degradation-penetration and hepatic stellate cells (HSCs) targeting on liver fibrosis therapy. In ECM barrier models, CHG micelles efficiently degraded pericellular collagen and demonstrated ECM penetration abilities, as well as displayed superior HSCs internalization. Moreover, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating cytokines, reversing the fibrotic liver to normal through various mechanisms. In conclusion, the developed fibrotic ECM degradation and HSCs targeting dual-functional nano-codelivery system provided a prospective potentiality in liver fibrosis therapy.
研究领域:
药理学
·
纳米技术
·
肝病学
·
药物递送系统
✓ 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）