Foods
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2022
·Vol. 11
·期 15
·2360
·
IF 5.561
Haiyan Zheng,Yu Pei,Yuan-Lin He,Yi Liu,Minqi Chen,Pengzhi Hong,Chunxia Zhou,Zhong-Ji Qian
Sulfated polysaccharides from red algae have a variety of biological activities, especially antitumor activities. Matrix metalloproteinase-9 (MMP-9) is a proteolytic metalloenzyme that degrades the central part of the extracellular matrix (ECM) and promotes tumor metastasis. In this research, we have investigated the influence and mechanism of GNP (sulfated polysaccharide fromGelidium crinale) on tumor metastasis and MMP-9 expression of human fibrosarcoma (HT1080) cells. The results inflected that the concentration of GNP below 100 μg/mL has no toxicity to HT1080 cells, but showed excellent activity in inhibiting cells migration and invasion. In addition, GNP effectively inhibits the mRNA of MMP-9 and reduces its expression and activity by regulating nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPK) and mTOR/PI3K/Akt signaling pathways. GNP has great potential as MMP-9 inhibitor and could be developed as a functional food or drug to prevent tumor metastasis.Keywords:sulfated polysaccharides;Gelidium crinale;MMP-9;migration;invasion
研究领域:
药理学
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肿瘤学
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海洋生物学
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Li Yali,Wang Jing,Huang Fenghong,Zhang Yufei,Zheng Mingming
The artificial multienzyme systems developed by mimicking nature has attracted much interest. However, precisely controlled compositions and ratios of multienzymatic co-immobilization systems are still limited by the indistinguishable nature of enzymes. Herein, a strategy for fabricating DNA-directed immobilization of horseradish peroxidase (HRP) and glucose oxidase (GOx) on hybrid DNA nanoflowers (GOx-HRP@hDFs) is presented. The preparation of micron-sized hybrid DNA flowers (hDFs) begins with the predetermined repeatable polymer-like DNA sequences which contained two strands. The hDFs structure is generated through one-pot rolling circle amplification (RCA) and self-assembly with magnesium pyrophosphate inorganic crystals. Based on the rigid-base pairing, GOx and HRP conjugated with sequences complementary to strands would be anchored to the predesigned locations, respectively. By adjusting the loading amount/ratio of enzymes properly, the maximal catalytic efficiency can be precisely regulated. The reaction activity of GOx-HRP@hDFs was 7.4 times higher than that of the free GOx-HRP under the optimal mole ratio (GOx/HRP 4:1). In addition, this multienzyme catalyst system exhibits excellent precision, specificity, reproducibility, and long-term storage stability when applied to real human blood samples. The preceding results validate that GOx-HRP@hDFs are promising candidates for personal diabetes detection.
研究领域:
生物化学
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纳米生物学
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医学诊断
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DOI
PubMed
高影响因子
Biomaterials Research
·
2022
·Vol. 26
·期 1
·1-21
·
IF 15.863
Wu Hao,Wei Guoli,Luo Lixia,Li Lingchang,Gao Yibo,Tan Xiaobin,Wang Sen,Chang Haoxiao,Liu Yuxi,Wei Yingjie,Song Jie,Zhang Zhenhai,Huo Jiege
Background Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear “cold” tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response.Methods In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological.Results Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment.Conclusion The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune “cold” 4T1 into “hot” tumors.
研究领域:
肿瘤学
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药学
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免疫学
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生物技术
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材料科学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Wei Ma,Huanli Zhang,Shuying Li,Zhiqiang Wang,Xiaodan Wu,Rui Yan,Fang Geng,Weijie Mu,Yingxue Jin
Chemodynamic therapy (CDT) based intracellular chemical reactions to produce highly cytotoxic reactive oxygen species has received wide attention. However, low efficiency of single CDT in weakly acidic pH and glutathione (GSH) overexpressed tumor cells has limited its clinical application. For this study were prepared two-dimensional metal–organic framework (MOF) to improve CDT efficiency based on the combined action of bimetallic CDT, consumption of overexpressed glutathione (GSH) in cells, folic acid (FA) induced tumor targeting and triphenylphosphine (TPP) induced mitochondrial targeting. With the use of Cu(II) as the central ion and tetrakis(4-carboxyphenyl)porphyrin (TCPP) as the ligand, two-dimensional Cu-MOF nanosheets were prepared, which were surface modified by manganese dioxide based on the in situ redox reaction between poly(allylamine hydrochloride) (PAH) and KMnO4 to obtain Cu-MOF@MnO2. Then FA and TPP were coupled with the nanosheets to form the title nanoplatform. Comprehensive physiochemical research has suggested that Cu(II) and MnO2 constituents in the nanoplatform could consume intracellular GSH and hydrogen peroxide to generate hydroxyl radicals through a Fenton-like reaction; meanwhile Cu(II) could undergo a Russell reaction to produce cytotoxic singlet oxygen. Detailed in vitro and in vivo biological experiments have revealed a good biosafety profile and a high tumor suppression effect. Therefore, the present research has realized multiple and efficient CDT effects with the aid of the sequential targeting of FA/TPP, also providing a strategy for the development of CDT drugs based on polymetallic organic frameworks.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2015
·
IF 6.409
Hailiang Huang,Shuo Shi,Xuyue Zheng,Tianming Yao
Based on specific homo-A/T DNA binding properties, a strategy for coralyne and mercury ions detection was realised by exonuclease-aided signal amplification . Coralyne could specifically bind homo-A DNA and protect it from the hydrolysis of exonuclease I. The coralyne-protected DNA was subsequently used as a trigger strand to hydrolyze DNA2 in exonuclease-aided signal amplification process. Thiazole orange was used to quantify the remainder DNA2. Under the optimal condition, the fluorescence intensity was linearly proportional to the concentration of coralyne in the range of 0.2–100 nM with a limit of detection (LOD) of 0.31 nM, which presented the lowest LOD for coralyne among all reported. With homo-T and Hg 2+ taking the place of homo-A DNA and coralyne, respectively, the system could also be used for Hg 2+ detection. The experiments in real samples also showed good results. This method was label-free, low-cost, easy-operating and highly repeatable for the detection of coralyne and mercury ions. It could also be extended to detect various analytes, such as other metal ions, proteins and small molecules by using appropriate aptamers.
研究领域:
分析化学
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生物化学
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环境科学
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DOI
PubMed
高影响因子
Polymer Chemistry
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2015
·Vol. 6
·期 11
·2098-2107
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IF 5.52
Yang Kang,Xiao-Mei Zhang,Sheng Zhang,Li-Sheng Ding,Bang-Jing Li
Self-assembly of stimuli-responsive polymeric nanoparticles have attracted great attention in recent years due to their prospective biological applications. This paper developed a novel pH-sensitive amphiphilic dendritic polyrotaxane drug-polymer conjugate by covalently linking doxorubicin (DOX) and dendritic polyrotaxane via a pH-responsible hydrazone bond with 1.84 wt% (weight percent) of DOX. The drug-polymer conjugate was amphiphilic and could be self-assembled to micelles (PR-g-DOX micelles) in an aqueous solution. The globular morphology and compact micelles with a diameter of around 110 nm were observed by SEM and TEM. Moreover, the micelles showed a significantly faster DOX release at mildly acidic pH of 6.0 and 5.0 and almost no burst release at the physiological pH of 7.4. Notably, it was confirmed that this micelle could efficiently deliver DOX to the nuclei of the tumor cells, which led to a much greater cytotoxic effects in the A549 cancer cells than the parent DOX. In vivo results revealed better drug tolerability of PR-g-DOX micelles and a higher in vivo efficacy without any increase in the toxicity of the PR-g-DOX micelles. Furthermore, the maximum tolerated dose (MTD) results showed that PR-g-DOX micelles showed an excellent safety profile with a two-fold higher MTD (10 mg kg−1 DOX) than that of free DOX (5 mg kg−1 DOX). We are convinced that the PR-g-DOX micelle has tremendous potentials for targeted cancer therapy.
研究领域:
药学
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生物医学工程
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肿瘤学
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DOI
高影响因子
Polymer Chemistry
·
2015
·Vol. 6
·期 15
·2945-2954
·
IF 5.52
Lei Xu,Lichao Liu,Feng Liu,Haibo Cai,Weian Zhang
Amphiphilic PNIPAM-b-PTPPC6MA block copolymers were first synthesized using porphyrin-containing monomers. The mono-hydroxylphenyl-triphenylporphyrin photosensitizer, TPP-OH, was modified into a porphyrin monomer, and it was further used to construct the amphiphilic PNIPAM-b-PTPPC6MA block copolymers using RAFT polymerization. PNIPAM-b-PTPPC6MA block copolymers can self-assemble into a plethora of morphologies ranging from spheres to vesicular aggregates and further to a single large vesicle. The PNIPAM-b-PTPPC6MA micelles exhibited a high singlet oxygen quantum yield. Moreover, confocal laser scanning microscopy (CLSM) and flow cytometry analysis confirmed that PNIPAM-b-PTPPC6MA micelles could effectively enhance the internalization rate in MCF-7 cells. According to the MTT assay, PNIPAM-b-PTPPC6MA micelles exhibited low dark toxicity and efficient PDT efficacy towards MCF-7 cells. Thus PNIPAM-b-PTPPC6MA block copolymers have the potential application for photodynamic therapy.
研究领域:
生物材料
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肿瘤学
·
高分子化学
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DOI
高影响因子
Nanoscale Research Letters
·
2017
·Vol. 12
·期 1
·1-8
·
IF 2.833
Wang Haiyan,Sheng Weizhong
Herein, folic acid (FA) conjugated Poly(d,l-lactide-co-glycolide) (PLGA)-lipid composites (FA-PL) were developed as nanocarriers for the targeted delivery of insoluble anti-cancer drug paclitaxel (PTX), resulting FA-PLP nanoparticles. Furthermore, 131 I, as a radioactive tracer, was used to label FA-PLP nanoparticles (FA-PLP- 131 I) to evaluate their cell uptake activity, in vivo blood circulation, and biodistribution. The FA-PLP- 131 I nanoparticles had a spherical morphology with great stability, a narrow size distribution (165.6 and 181.2 nm), and −22.1 mV in average zeta potential. Confocal laser scanning microscopy indicated that the targeting molecule FA promotes PLP- 131 I uptake by melanoma B16F10 cells, which was further confirmed by the cell incorporation rate via 131 I activity detection as measured by a gamma counter. FA-PLP- 131 I without PTX (FA-PL- 131 I) shows minor cytotoxicity, good biocompatibility, while FA-PLP- 131 I was demonstrated to have efficient cell viability suppression compared to free PTX and PLP- 131 I. Following intravenous injection, the blood circulation half-life of free PTX ( t
1/2 = 5.4 ± 0.23 h) was prolonged to 18.5 ± 0.5 h by FA-PLP- 131 I. Through FA targeting, the tumor uptake of FA-PLP- 131 I was approximately 4.41- and 12.8-fold higher compared to that of PLP- 131 I and free PTX- 131 I, respectively. Moreover, following 40 days of treatment, FA-PLP- 131 I showed an improved tumor inhibition effect compared to free PTX and PLP- 131 I, with no relapse and no remarkable systemic in vivo toxicity. The results demonstrate that the 131 I-labeled PLGA-lipid nanoparticle can be simultaneously applied for targeted drug delivery and reliable tracking of drugs in vivo.
研究领域:
药学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
·
IF 3.887
Yiwen Dong,Hui Ye,Yi Liu,Lihua Xu,Zuosu Wu,Xiaohui Hu,Jianfeng Ma,Janak L. Pathak,Jinsong Liu,Gang Wu
Peri-implant infection control is crucial for implant fixation and durability. Antimicrobial administration approaches to control peri-implant infection are far from satisfactory. During bacterial infection, pH level around the peri-implant surface decreases as low as pH 5.5. This change of pH can be used as a switch to control antimicrobial drug release from the implant surface. Silver nanoparticles (AgNPs) have broad-spectrum antimicrobial properties. In this study, we aimed to design a pH-dependent AgNPs releasing titania nanotube arrays (TNT) implant for peri-implant infection control. The nanotube arrays were fabricated on the surface of titanium implant as containers; AgNPs were grafted on TNT implant surface via a low pH-sensitive acetal linker (TNT-AL-AgNPs). SEM, TEM, AFM, FTIR as well as XPS data showed that AgNPs have been successfully linked to TNT via acetal linker without affecting the physicochemical characteristics of TNT. The pH 5.5 enhanced AgNPs release from TNT-AL-AgNPs implant compared with pH 7.4. AgNPs released at pH 5.5 robustly increased antimicrobial activities against gram-positive and gram-negative bacteria compared with AgNPs released at pH 7.4. TNT-AL-AgNPs implant enhanced osteoblast proliferation, differentiation, and did not affect osteoblast morphology in vitro . In conclusion, incorporation of AgNPs in TNT via acetal linker maintained the surface characteristics of TNT. TNT-AL-AgNPs implant was biocompatible to osteoblasts and showed osteoinductive properties. AgNPs were released from TNT-AL-AgNPs implant in high dose at pH 5.5, and this release showed strong antimicrobial properties in vitro . Therefore, this novel design of low pH-triggered AgNPs releasing TNT-AL-AgNPs could be an infection-triggered antimicrobial releasing implant model to control peri-implant infection.
研究领域:
生物医学工程
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材料科学
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微生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
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2017
·
IF 2.673
Lei Meng,Quan Zhu,Jian-Hang Yin,Na Xu
A simple luminescence sensor, based on polyethyleneimine protected silver nanoclusters (AgNCs@PEI) is successfully fabricated via one-pot reduction method. The obtained AgNCs@PEI are characterized by high-resolution transmission electron microscopy (HR-TEM), Dynamic light scattering (DLS), transient and steady-state fluorescence, and UV–vis spectroscopy. The NCs show large Stocks-shift (∼ 130 nm), high tolerability to extreme pH and high ionic strengths , and excellent photo-stability under UV irradiation , laying the basement for the practical applications. In addition, the sensor is used to detect the Co 2 + basing on the luminescence quenching , which is interfered by pH conditions (from pH 4.0 to pH 7.4). As a luminescence probe for Co 2 + ions, the detection limit of AgNCs@PEI is as low as 0.25 nM, which is much lower than that of many other reports. Additionally, the AgNCs@PEI possess the advantages of good selectivity, fast response and abroad linear detection. A linear response range in 0.5 nM–50 μM is achieved for Co 2 + when using 20 μM AgNCs@PEI in BR buffer solution (neutral condition pH 7.4). Incubation time of AgNCs@PEI toward Co 2 + is only 2 min and it can distinguish Co 2 + from other 13 metal ions . Furthermore, the probe (AgNCs@PEI) is applied to sensing and imaging of HeLa cells, showing low cytotoxicity and good sensitivity.
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PubMed
高影响因子
Advanced Healthcare Materials
·
2017
·Vol. 6
·期 18
·1700354
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IF 5.11
Yongjiu Lv,Yang Cao,Pan Li,Jianxin Liu,Huali Chen,Wenjing Hu,Liangke Zhang
A multifunctional drug delivery vehicle, which combines the active targeted mesoporous silica nanoparticle (MSN) and microbubble (MB) drug delivery system, is proposed and fabricated. The resulting delivery vehicle integrates the merits of high drug loading capacity, multitargeting, and ultrasound-guided releasing. Folate (FA), which serves as an active ligand, is modified to the surface of MSN (MSN-FA) to enhance cell membrane translocation. MSN-FA is loaded with tanshinone IIA (TAN), then encapsulated in a microbubble (denoted as MSN-FA-TAN-MB) for more precise tumor targeting. The conjunction between FA and MSN is confirmed by fourier transform infrared spectroscopy (FTIR). The characteristics and morphology of MSN-FA-TAN-MB are investigated by confocal microscopy and transmission electron microscopy. In vitro cytotoxicity and cellular uptake studies of MSN-FA-TAN-MB are conducted on A549 and HeLa tumor cells. FA-facilitated MSN-FA-TAN uptake is shown by HeLa cells that overexpress FA receptors via a FA-receptor-mediated endocytosis mechanism. The ultrasound response property of MSN-FA-TAN-MB is also verified. MSN-FA-TAN-MB shows significant antitumor efficacy in vivo with the assistance of FA, MB, and an external ultrasound irradiation. Thus, this multifunctional vehicle may provide a novel strategy for tumor targeting and imaging in tumor therapy.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 66
·41779-41786
·
IF 3.108
Zhou Yang,Fan Wu,Hongjie Yang,Ping Zhou
A novel protein tyrosine phosphatase 1B (PTP1B) inhibitor, FYGL, extracted from Ganoderma lucidum, was first reported to have an efficient hypoglycemic effect and high safety in vivo in our previous study. However, the underlying mechanism of the anti-diabetes activity was still unclear. The dominant effective component of FYGL was demonstrated to be a neutral hyperbranched proteoglycan macromolecule. Therefore, it is necessary to first elucidate how the biomacromolecule works at the cellular level, in order to understand its possible functional mechanism in vivo. Herein, we focused on demonstrating the cell internalization and endocytosis mechanism of FYGL in HepG2 cells. A series of cellular uptake pathways was explored, including clathrin-mediated endocytosis, caveolae/lipid-mediated endocytosis, and macropinocytosis. Confocal laser scanning microscopy and flow cytometry were used to demonstrate the absorption of FYGL by HepG2 cells. Furthermore, pharmacologically selective inhibitors and Western blot methods were used to demonstrate that macropinocytosis mediated by c-Src/PI3K cascades was the preferred route for the uptake of FYGL in cells. Our study provided the basis of uptake of FYGL for an efficient hypoglycemic effect. The functional mechanism of the signaling pathway in vivo will be reported in the future.
研究领域:
药理学
·
细胞生物学
·
分子生物学
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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）