ANALYST
·
2023
·Vol. 148
·期 10
·2352-2361
·
IF 4.2
Xiwen Li,Peiran Meng,Mingyang Sun,Yue Chen,Zhiyi Song,Xinyao Wang,Na Li,Yue Sun
Phospholipase C (PLC) has important biological functions in specific cancer types, immune disorders and neurodegeneration. Here, an ultrasensitive electrochemical sensor for PLC was developed via signal amplification based on breathing atom transfer radical polymerization (ATRP). First, phosphatidylethanolamine (PE) was immobilized on the surface of a gold electrode by L-cysteine and cross-linker. Then, PE was specially hydrolyzed by PLC to obtain the phosphate groups and tethered with the ATRP initiator α-bromophenacetic acid (BPAA) by the coordination action of Zr4+. After the breathing ATRP, a large number of electroactive monomers (ferrocenylmethyl methacrylate, FcMMA) were successfully grafted from BPAA. The experimental results indicated that the detection signal of the obtained electrode (sensor) was proportional to the concentration of PLC. The sensor showed a low detection limit of 0.270 U L−1 and a wide linear range of 1–40 U L−1 (R2 = 0.997). Most importantly, the sensor was successfully applied to detect PLC in breast cancer cells (MCF-7, MDA-MB-231) and nontumor cells (MCF-10A). The value obtained by our electrochemical sensor had no obvious difference from that determined by the commercial ELISA kit. These results showed that the fabricated PLC sensor had acceptable potential in clinical applications.
研究领域:
生物化学
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生物技术
·
分析化学
·
癌症研究
·
免疫学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-17
·
IF 10.6
Chen Wenting,Hu Fangfang,Gao Qian,Zheng Caiyun,Bai Que,Liu Jinxi,Sun Na,Zhang Wenhui,Zhang Yanni,Dong Kai,Lu Tingli
Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.Graphical Abstract
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Rong Sun,Song Shen,Yun-Jiao Zhang,Cong-Fei Xu,Zhi-Ting Cao,Long-Ping Wen,Jun Wang
Cancer stem cells (CSCs) have garnered increasin g attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced ‘stemness’ and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH hi cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH hi MDA-MB-231 cells in vitro . Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH hi cells. More importantly, compared with single treatment, the combined delivery systems NP CQ /NP DOX and NP CQ/DOX (NP CQ /NP DTXL and NP CQ/DTXL ) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs ( p < 0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer.
研究领域:
肿瘤学
·
药理学
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纳米技术
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癌症生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2013
·Vol. 15
·期 10
·1-10
·
IF 2.175
Li Jia,An Yan-Li,Zang Feng-Chao,Zong Shen-Fei,Cui Yi-Ping,Teng Gao-Jun
We report a composite nanoprobe based on silica-coated magnetic nanoparticles (NPs) for distinguishing breast cancers at different HER2 statuses. The nanoprobe has a core–shell structure, with Fe 3 O 4 NPs as the magnetic core and dye-embedded silica as the fluorescent shell, whose average size is about 150 nm. Besides, the outmost surfaces of the probes were modified with specific antibodies to endow the probe with a targeting ability. With such a structure, the nanoprobe can accomplish dual mode targeting of human breast cancer cells based on fluorescence and magnetic resonance imaging (MRI). In the experiments, three human breast cancer cell lines were used to test the targeting ability of the nanoprobe. Specifically, SKBR3 cells with a high HER2 expression level were used as the model target cells, while MCF7 cells with a lower HER2 expression levels and HER2-negative MDA-MB-231 cells were used as the controls. Both the fluorescence and MRI imaging results confirmed that the nanoprobe can distinguish three cancer cell lines with different HER2 expression levels. With the dual mode imaging and specific targeting properties, we anticipate that the presented nanoprobe may have a great potential in the diagnosis and treatment of cancerous diseases.
研究领域:
癌症研究
·
纳米技术
·
医学成像
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Chao Wang,Xiaodan Jia,Wenyao Zhen,Mengchao Zhang,Xiue Jiang
In this article, a type of small-sized metal organic framework (MOF), MIL-101(Fe), as an intelligent delivery system was fabricated to load chemotherapy drug dihydroartemisinin (DHA) and photosensitizer methylene blue (MB). In addition, the Fe ions releasedfrom the MOFs in the tumor environment not only enhanced the curative effect of DHA but also catalyzed H2O2 to release O2, which further improved the photodynamic therapeutic effect of the nanocomposites. The nanocomposites can serve as a T2 magnetic resonance imaging contrast agent at the same time. The polylactic acid (PLA) and polyethylene glycol (PEG) were used to modify the surface of MOFs-MB-DHA to acquire the excellent controllable release of drugs and good biocompatibility to decrease the side effects for normal cells. All the results show remarkably increase of the therapeutic efficiency by synergistic chemo-photodynamic therapy. Thus, a smart multifunctional drug delivery system for diagnosis and therapy based on MOFs-MB-DHA@PLA@PEG was constructed for not only real-time imaging but also chemotherapy and photodynamic synergetic therapy to kill the tumor selectively, showing great potential for conquering the existing barrier in chemo-photodynamic synergetic therapy.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
材料科学
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治疗诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 1
·171
·
IF 2.861
Xiangcong Wang,Maocai Yan,Qibao Wang,Huannan Wang,Zhengyang Wang,Jiayi Zhao,Jing Li,Zhen Zhang
Indole-2-carboxylic acid copper complex (ICA-Cu) was successfully prepared and characterized through elemental analysis, IR, UV-Vis,1H-NMR, TG analysis, and molar conductance, and its molecular formula was [Cu2(C9H6O2N)4(H2O)2]·2H2O. The binding ability of ICA-Cu to calf thymus DNA (CT-DNA) was examined by fluorescence spectrometry and the viscosity method. The results indicated that, upon the addition of increasing amounts of CT-DNA, the excitation and emission intensity of ICA-Cu decreased obviously and the excitation spectra shifted towards a long wavelength. ICA-Cu could displace ethidium bromide (EB) from the EB-DNA system, making the fluorescence intensity of the EB-DNA system decrease sharply; the quenching constantKSVvalue was 3.99 × 104M−1. The emission intensity of the ICA-Cu-DNA system was nearly constant, along with the addition of Na+in a series of concentrations. The fluorescence of the complex could be protected after the complex interacted with DNA. A viscosity measurement further supported the result that the ICA-Cu complex may interact with DNA in an intercalative binding mode. The antioxidant activities of ICA-Cu were evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, a hydroxyl radical (OH) scavenging assay, and a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay. The ICA-Cu exhibited the highest inhibitory effects on the ABTS radical (94% inhibition at 60 µM), followed by OH and DPPH radicals (the degrees of inhibition being 71% and 56%, respectively). The in vitro cytotoxicity activity of ICA-Cu against two human breast cancer cell lines, MDA-MB-231 and MCF-7, was investigated by 3-[4,5-dimethyltiazol2-yl]-2.5-diphenyl-tetrazolium bromide (MTT) assay and cellular morphological analysis. The results showed that, upon increasing the concentration of ICA-Cu, an increase was observed in growth-inhibitory activity and the inhibition percentage were greater than 90% at 20 µM in both cell lines. Also, cellular morphological changes in the two cell lines agreed with the cytotoxicity results.Keywords:DNA-binding;antioxidant;anticancer;indole-2-carboxylicacid;copper(II) complexes
研究领域:
化学
·
生物化学
·
药理学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED ELECTROCHEMISTRY
·
2022
·Vol. 53
·期 3
·547-557
·
IF 2.925
Hu Kaiyue,Ren Xinxin,Qin Lingxia,Guo Zhiyong,Wu Di,Wang Sui,Hu Yufang
The purpose of this study was to achieve a specific unlocking of the butterfly effect: nanointerface-based electrochemical biosensing of adenosine triphosphate (ATP) and alkaline phosphatase (ALP). Based on the Faraday-cage concept reported first by our group, we built a new outer Helmholtz plane (OHP)-based electrochemical biosensor by using an unique nanocomposite involving three-dimensional graphene-Au nanoparticles (3D-GO-AuNPs), tetrahedral DNA nanostructures (TDNs), and separated ATP aptamers, in which methylene blue (MB) was employed as the electrochemical signal output. In this process, the prepared nanocomposites were attached favorably onto the TDN substrate electrode surface due to the interaction of ATP and its aptamer, creating a better OHP of the electrode owing to its large enough specific surface area; then a detection limit of 0.25 pM was calculated by 3 δ /slope. Whereas, the hydrolysis for ATP of ALP can hinder this binding process, therefore, the biosensor could be indirectly applied for ALP analysis with a detection limit of 0.21 mU/L (3 δ /slope). Since some small changes of the two targets will set off a whole series of changes in system, the OHP-extended biosensor provides a superior electrochemical platform for complex biological processes with causal relationships in clinical diagnosis and drug development, similar to the butterfly effect. Graphical abstract
研究领域:
生物化学
·
纳米技术
·
电化学
·
临床诊断
✓ 已验证
DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2024
·Vol. 47
·期 21
·e70014
·
IF 2.8
Binhong He,Fengying Ye,Jieqing Feng,Ting Zhou
Lipid extraction of complex biological samples is essential for high-quality data in liquid chromatography-mass spectrometry (LC-MS)-based lipidomics. This study introduces a three-phase liquid extraction (3PLE)-ultra-high-performance LC coupled with quadrupole time-of-flight tandem MS method. This method was successfully applied to lipidomics analysis of breast cancer cells, including highly metastatic MDA-MB-231 and slightly metastatic MCF7 cells. The 3PLE method employed an n -hexane/methyl tert-butyl ether/acetonitrile/water solvent system that formed one aqueous and two organic phases. Neutral and polar lipids were enriched in the upper and middle organic phases, respectively, and combined for detection, thereby reducing analysis time. Compared with the Bligh and Dyer method, 3PLE achieved higher sensitivity and detected more features, with over a 50% increase in the relative abundance of nearly 50% of the differential lipids. In total, 21 differential lipids were identified in the MDA-MB-231 group and 22 in the MCF7 group compared to normal breast epithelial cells (MCF10A). Pathway analysis suggested that lipid changes in breast cancer cells were associated with glycerophospholipid metabolism, arachidonic acid metabolism, sphingolipid metabolism, and linoleic acid metabolism. The study presents a highly efficient lipidomics method, providing a scientific foundation for understanding breast cancer pathogenesis and aiding in diagnosis.
研究领域:
癌症生物学
·
分析化学
·
质谱分析
·
脂质代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Guiqin Huang,Yawen Cai,Menghui Ren,Xiaoyu Zhang,Yu Fu,Run Cheng,Yingdi Wang,Mingxing Miao,Lingpeng Zhu,Tianhua Yan
Introduction Triple-negative breast cancer (TNBC) is the primary cause of breast cancer-induced death in women. Literature has confirmed the benefits of Salidroside (Sal) in treating TNBC. However, the study about potential therapeutic targets and mechanisms of Sal-anchored TNBC remains limited. Objective This study was designed to explore the main targets and potential mechanisms of Sal against TNBC. Methods Network pharmacology, bioinformatics, and machine learning algorithm strategies were integrated to examine the role, potential targets, and mechanisms of the Sal act in TNBC. MDA-MB-231 cells and tumor-bearing nude mice were chosen for in vitro and in vivo experimentation. Cell viability and cytotoxicity were determined using CCK-8, LDH test, and Calcein-AM/PI staining. Antioxidant defense, lipid peroxidation, and iron metabolism were explored using glutathione, glutathione peroxidase, malondialdehyde (MDA), C11-BODIPY 581/591 probe, and FerroOrange dye. Glutathione peroxidase 4 (GPX4) or stearoyl-CoA desaturase 1 (SCD1) overexpression or nuclear receptor co-activator 4 (NCOA4) deficiency was performed to demonstrate the mechanism of Sal on TNBC. Results The prediction results confirmed that 22 ferroptosis-related genes were identified in Sal and TNBC, revealing that the potential mechanism of the Sal act on TNBC was linked with ferroptosis. Besides, these genes were mainly involved in the mTOR, PI3K/AKT, and autophagy signaling pathway by functional enrichment analysis. The in vitro validation results confirmed that Sal inhibited TNBC cell proliferation by modulating ferroptosis via elevation of intracellular Fe 2+ and lipid peroxidation. Mechanistically, Sal sensitized TNBC cells to ferroptosis by inhibiting the PI3K/AKT/mTOR axis, thereby suppressing SCD1-mediated lipogenesis of monounsaturated fatty acids to induce lipid peroxidation, additionally facilitating NCOA4-mediated ferritinophagy to increase intracellular Fe 2+ content. The GPX4 or SCD1 overexpression or NCOA4 deficiency results further supported our mechanistic studies. In vivo experimentation confirmed that Sal is vital for slowing down tumor growth by inducing ferroptosis. Conclusions Overall, this study elucidates TNBC pathogenesis closely linked to ferroptosis and identifies potential biomarkers in TNBC. Meanwhile, the study elucidates that Sal sensitizes TNBC to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy, regulated by PI3K/AKT/mTOR signaling pathways. Our findings provide a theoretical basis for applying Sal to treat TNBC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Tian Sang,Yan Zhong,Chao-Hao Hu,Dian-Hui Wang,Tao Huang,Sheng Jiang,Hao Liu,Wen-Yi Wang,Ni-Ni Wei
A novel SrCu□O□ photocatalyst containing Cu vacancy and O vacancy was synthesized for the first time based on solid-phase sintering. The crystal structure, elemental composition, microscopic morphology, optical properties and energy band structure of the samples were characterized and analyzed in detail. The vacancies in the material were determined by ICP-MS and EPR, first-principles calculations showed that the introduction of vacancies extends the forbidden band of the photocatalytic to the visible band. The photocatalytic performance of SrCu□O□ was evaluated by degrading MB and TC HCI. Our results show that SrCu□O□ enhances the degradation performance of organic compounds due to rich vacancies that promote electron-hole pair separation and improve photogenerated carrier separation efficiency. Vacancy-containing metal oxide catalysts have broad application value in environmental remediation.
研究领域:
材料科学
·
环境科学
·
化学
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2021
·
IF 4.86
Jie Tang,Mingrong Bei,Jia Zhu,Guangtao Xu,Deqing Chen,Xin Jin,Jianzhong Huang,Jingjian Dong,Lili Shi,Long Xu,Bo Hu
Cadmium (Cd) exposure can exert an impact on carcinogenicity of breast cancer, however, the mechanism is not fully understood in triple-negative breast cancer (TNBC). We performed a TNBC MDA-MB-231 cell model and assessed the toxic effect of Cd exposure (0, 10, 20, 50, 60, 80 μM). Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Lactate dehydrogenase (LDH) release, apoptosis and pyroptosis were increased, which were relieved by z-VAD. Elevated ROS and NLRP3, caspase-1, IL-1β and IL-18 were detected, which was attenuated by N-acetylcysteine. Increased bax and decreased caspase-8, caspase-9 and caspase-3 were found. gasdermin E (GSDME) was activated with cleavage of GSDME-NT, which was retarded by z-VAD. Additionally, p38 MAPK signaling pathway was activated. Our data demonstrate GSDME-activated pyroptosis in Cd toxicity, implying a potential impact on TNBC.
研究领域:
毒理学
·
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Yunfan Zhou,Xue Wei,Jun Chen,Hanzhi Xiong,Dandan Sui,Xu Chen,Wensheng Yang
Breast cancer is a malignant tumor, with various subtypes showing different behaviors. Endogenous H2O2 is an important marker of tumor progression, which makes it important to study the relationship between breast cancer subtypes and H2O2 for pathogenesis and treatment strategies, but this has rarely been reported so far. In this work, we constructed a three-dimensional (3D) electrochemiluminescence (ECL) sensing platform for the detection of H2O2 released from two typical subtypes of breast cancer cells (MCF-7 cells for luminal A-type and MDA-MB-231 cells for three negative breast cancers, TNBCs). To adequately replicate the tumor microenvironment, the peptide hydrogel was introduced as a scaffold for 3D cell culture. The titanium foam (TF) was used as a 3D electrode to better match the 3D culture substrate. N-(4-Aminobutyl)-N-ethylisoluminol (ABEI) was selected as the ECL emitter and assembled into the peptide hydrogel by hydrogen bonding and π-stacking, which resulted in a stable and homogeneous distribution of ABEI along the hydrogel fibers. Furthermore, basic amino acids were introduced to provide alkaline microenvironment for ABEI. Therefore, ABEI exhibited high ECL efficiency, resulting in a high sensitivity with an ultralow detection limit of 0.023 nM (S/N = 3) for H2O2 of the proposed ECL biosensor. MCF-7 and MDA-MB-231 cells were cultured in a 3D peptide hydrogel/ABEI/TF electrode, respectively, and endogenous H2O2 was successfully monitored. A notably significant difference of H2O2 released between MDA-MB-231 cells and MCF-7 cells without stimulation but similar extra release with stimulation were observed. These findings may help understand the physiological mechanisms behind the various subtypes and reactive oxygen species (ROS)-related treatment for breast cancer.
研究领域:
生物医学工程
·
癌症生物学
·
分析化学
·
细胞生物学
✓ 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）