ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Qunfei Tai,Hailong Yu,Mingxia Gao,Xiangmin Zhang
From metabolic waste to biological mediators, exosomes have emerged as the key player in a variety of pathological processes, particularly in oncogenesis. The exosome-mediated communication network involves nearly every step of cancer progression, promoting the proliferation and immune escape of cancer cells. Therefore, the removal of cancer-derived exosomes has profound clinical significance. Current methods for exosome separation and enrichment are either for large-scale samples or require complex pretreatment processes, lacking effective methods for trace-volume exosome capture in situ. Herein, we have developed an in situ exosome capturing and counting device based on the antibody-functionalized capillary. Specific antibodies targeting exosome biomarkers were immobilized to the inner wall of the capillary via biotin-streptavidin interaction for direct cancer exosome capturing. Subsequent exosome staining enabled imaging and enumeration. Acceptable linearity and reproducibility were achieved with our device, with the capturing and detective range between 3.3 × 104 and 3.3 × 108 particles, surpassing the nanoparticle tracking analysis by 2 orders of magnitude while requiring merely 30 μL sample. We demonstrated that MCF-7-derived exosomes induced epithelial–mesenchymal transition of epithelial cells MCF-10A, and our method was able to completely or partially reverse the transition by complete depletion or specific depletion of cancer exosomes without any preprocessing. Moreover, both whole exosomes and cancer-specific exosomes alone from mimic blood samples were successfully captured and counted, without obvious non-specific adsorption. In all, our approach realized the in situ depletion and number-counting of cancer-derived exosomes directly from the complex humoral environment, having the potential to provide a comprehensive tumor therapeutic and prognosis evaluation tool by targeted hemodialysis and counting of tumor-derived exosomes.
研究领域:
肿瘤学
·
生物技术
·
纳米技术
·
细胞生物学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 3.7
Lingke Feng,Rong Pan,Ke Ning,Wen Sun,Yirong Chen,Yuanyuan Xie,Mingzhu Wang,Yan Li,Ling Yu
Cell motility is crucial in cancer metastasis, and understanding its regulation in tumor cells is vital for developing anti-metastatic therapies. Traditional 2D cell culture assays provide insights into cell migration but fail to replicate the complex 3D architecture of tissues in vivo . 3D cell culture models like tumor spheroids have been applied for cell migration tests. This study investigates the role of spheroid maturity in tumor cell motility, hypothesizing that spheroid maturity mirrors physiological conditions in solid tumors. Human prostate (DU145), breast (MCF-7), and murine breast (EMT-6) cancer cells were cultured into spheroids of varying ages (3, 7, and 11 days). The migration and invasion of these spheroids were analyzed, revealing that 11-day-old DU145 spheroids demonstrated the greatest horizontal migration, correlating with RNA-seq data showing increased cell adhesion, cytoskeleton dynamics, and motility pathways. Confocal microscopy and single-cell analysis indicated higher reactive oxygen species (ROS) levels in mature spheroids, potentially activating motility pathways. Additionally, DU 145 spheroids were treated with chemotherapy reagent Doxorubicin (DOX), and the results showed that spheroids culture for 7 and 11 days exhibited greater resistance to DOX compared to spheroids cultured for 3 days. These findings highlight the importance of considering spheroid maturity in cancer research and drug development, emphasizing the need for systematic analysis of spheroid growth conditions to ensure reproducible and reliable experimental settings.
研究领域:
癌症生物学
·
细胞生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Nianzu Liu,Jingyao Song,Yanwei Lu,Jason J. Davis,Fengxian Gao,Xiliang Luo
The rapid, convenient, and selective assaying of clinical targets directly in complex biological media brings with it the potential to revolutionize diagnostics. One major hurdle to impact is retention of selectivity and a tight control of nonspecific surface interactions or biofouling. We report herein, the construction of an antifouling interface through the covalent attachment of designed branched zwitterionic peptides onto electrodeposited polyaniline film. The antifouling capability of the designed branched peptide significantly outperforms that of the commonly used PEG and linear peptides. The interfaces modified with branched peptides are exceptionally effective in reducing a nonspecific protein and cell adsorption, as verified by electrochemical and fluorescent characterization. The derived sensors with mucin1 protein (MUC1) aptamer as the recognition element detect MUC1-positive MCF-7 breast cancer cells in human serum with high sensitivity and selectivity. The linear response range of the cytosensor for the MCF-7 cell is from 50 to 106 cells/mL, with a limit of detection as low as 20 cells/mL. More importantly, the assaying performances remain unchanged in human serum owing to the presence of branched antifouling peptide, indicating feasibility of the cytosensor for practical cancer cell quantification in complex samples.
研究领域:
生物传感器
·
癌症诊断
·
材料科学
·
分析化学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ChemMedChem
·
2016
·Vol. 12
·期 3
·235-249
·
IF 2.98
Silong Zhang,Zhiyong Wang,Zhiye Hu,Changhao Li,Chu Tang,Kathryn E. Carlson,Junjie Luo,Chune Dong,John A. Katzenellenbogen,Jian Huang,Hai-Bing Zhou
Graphical Add a new element ! This is the first report of selenophene-core compounds as estrogen receptor (ER) ligands. In transcription assays, several selenophenes were profiled as superagonists for ERα; moreover, a few selenophenes exhibited antiproliferative activity similar to that of 4-hydroxytamoxifen in MCF-7 breast cancer cells while being nontoxic toward normal VERO cells. These new ligands could act as models for the development of novel agents leading to improved therapeutics that target the ER. The importance of the heterocyclic core elements with peripheral phenolic and alkyl substituents as a dominant structural motif of ligands for the estrogen receptor (ER) has been well recognized. In this study we expanded the structural diversity of core elements by preparing selenium-containing heterocycles and exploring the activities of these selenophenes on the two ERs, ERα and ERβ. Careful structure–activity relationship (SAR) analysis of their ER binding affinities showed that most selenophenes are ERβ-selective, with the position of the phenol substituents on the selenophene core and the nature of these substituents having a marked effect on their binding affinities. The compound bis(2-fluoro-4-hydroxyphenyl)selenophene ( 2 f ) has the highest relative binding affinity (RBA) of 24.3 for ERβ. In transcription assays, most selenophenes were found to exhibit partial to full agonist activity for both ER subtypes, with compounds bis(2-methyl-4-hydroxyphenyl)selenophene ( 2 b ), bis(4-fluoro-3-hydroxyphenyl)3-bromoselenophene ( 6 f ), and 2,3,5-tris(hydroxyphenyl)thiophenes ( 8 b and 8 d ) profiling as superagonists for ERα; however, several compounds display a range of ERα or ERβ antagonistic activities. A few selenophenes exhibited antiproliferative activity, with compound 8 c showing antiproliferative effects similar to that of 4-hydroxytamoxifen in breast cancer MCF-7 cells while being nontoxic to normal VERO cells. These new ligands could act as models for the development of novel agents leading to improved therapeutics that target the estrogen receptor.
研究领域:
药理学
·
化学
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Danni Liu,Yaoqi Wang,Qi Sun,Dong Mei,Xiaoling Wang,Yan Su,Jie Zhang,Ran Huo,Yang Tian,Siyu Liu,Shuang Zhang,Chunying Cui
Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.
研究领域:
癌症治疗
·
纳米技术
·
基因递送
·
细胞生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Chen Jieying,Zhao Chan,Liu Hao,Wang Zhangchao,Ma Luyao,Zhang Jiamin,Xu Ning,Hu Ke,Duan Lei
Phase-change droplets (PCDs) are intelligent responsive micro and nanomaterials developed based on micro/nano bubbles. Subject to external energy inputs such as temperature and ultrasound, the core substance, perfluorocarbon (PFC), undergoes a phase transition from liquid to gas. This transformation precipitates alterations in the PCDs’ structure, size, ultrasound imaging capabilities, drug delivery efficiency, and other pertinent characteristics. This gives them the ability to exhibit “intelligent responses”. This study utilized lipids as the membrane shell material and perfluorohexane (PFH) as the core to prepare lipid phase-change droplets. Superparamagnetic nanoparticles (PEG-functionalized Fe3O4 nanoparticles) and the anti-tumor drug curcumin (Cur) were loaded into the membrane shell, forming magnetic drug-loaded phase-change droplets (Fe-Cur-NDs). These nanoscale phase-change droplets exhibited excellent magnetic resonance/ultrasound imaging capabilities and thermal/ultrasound-mediated drug release. The Fe-Cur-NDs showed excellent anti-tumor efficacy for the MCF-7 cells under low-intensity focused ultrasound (LIFU) guidance in vitro. Therefore, Fe-Cur-NDs represent a promising smart responsive theranostic integrated micro/nano drug delivery system.
研究领域:
生物医学工程
·
纳米技术
·
药学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2020
·
IF 2.169
Yutong Wang,Yanfang Ding,Changyuan Wang,Meng Gao,Youwei Xu,Xiaodong Ma,Xinyi Ma,Hongxia Cui,Lei Li
Fenretinide (4-HPR), a synthetic retinoid, has shown its antitumor activity in many tumor types with low cytotoxicity to normal cells and high clinical safety. However, the low water solubility limits its further biological applications. To increase solubility, 4-HPR was conjugated with methoxy polyethylene glycol carboxylic acid (mPEG2K-COOH) by an ester linkage between the phenol hydroxyl of 4-HPR and the carboxyl of mPEG2K-COOH. The 4-HPR-PEG2K conjugate micelles had mean size of 76.70 ± 1.248 nm with a narrow distribution and a low critical micelle concentration. In vitro cytotoxicity studies showed the micelles have higher cytotoxicity to A2780s and MCF-7 cells. Its IC50 was 4.7 and 4.1-fold lower than the free 4-HPR, respectively. Importantly, in vivo pharmacokinetic studies, the AUC of 4-HPR was found to be 2.3-fold higher in 4-HPR-PEG2K micelles compared to free 4-HPR. And the 4-HPR-PEG2K micelles had higher antitumor activity. Meanwhile, the histopathology analysis exhibited that the micellar treatment decreased the viability of A2780s cells and increased the level of induced apoptosis. Therefore, the enhanced activity of 4-HPR by the method of conjugation with mPEG2K-COOH could hopefully provide new insights into the matter of ovarian cancer and breast cancer treatment.
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Shumeng Zhang,Shiyi Deng,Yuan Luo,Dawei Tang,Fangzhen Wang,Gen He
Intracellular hydrogen peroxide (H 2 O 2 ) plays a crucial role in regulating various biological processes including cell proliferation, apoptosis, and immune response. Driven by the remarkable need for determination of intracellular H 2 O 2 with higher precision and sensitivity, a novel ternary nanocomposite electrode integrating silver nanoparticles (AgNPs)/Polyoxometalates (POMs)/three-dimensional graphene foam (3DGF) was fabricated for real-time detection of H 2 O 2 generated in MCF-7 cells. POMs acted like an artificial peroxidase, together with AgNPs that served as electron mediator to amplify the electrochemical signal were successfully loaded on the surface of 3DGF, which significantly improved the detection sensitivity due to synergistic advantages. The tricomponent nanohybrids modified glass carbon electrode (AgNPs@POMs-3DGF/GCE) showed a high sensitivity toward reduction of H 2 O 2 , and meanwhile had good long-term stability, wide linear range and low detection limit. Real-time detection of H 2 O 2 released from MCF-7 cells stimulated by N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) had been demonstrated using the chronoamperometry based on AgNPs@POMs-3DGF/GCE, which showed a quick response and excellent specificity to H 2 O 2. It was expected that the AgNPs@POMs-3DGF/GCE was able to monitor H 2 O 2 during the dynamic biological process involving H 2 O 2 metabolism.
研究领域:
分析化学
·
纳米技术
·
生物电化学
·
材料科学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Oncotarget
·
2016
·
IF 5.008
Li Lv,Chunxia Liu,Chuxiong Chen,Xiaoxia Yu,Guanghui Chen,Yonghui Shi,Fengchao Qin,Jiebin Ou,Kaifeng Qiu,Guocheng Li
The combination of a chemotherapeutic drug with a chemosensitizer has emerged as a promising strategy for cancers showing multidrug resistance (MDR). Herein we describe the simultaneous targeted delivery of two drugs to tumor cells by using biotin-decorated poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles encapsulating the chemotherapeutic drug doxorubicin and the chemosensitizer quercetin (BNDQ). Next, the potential ability of BNDQ to reverse MDR in vitro and in vivo was investigated. Studies demonstrated that BNDQ was more effectively taken up with less efflux by doxorubicin-resistant MCF-7 breast cancer cells (MCF-7/ADR cells) than by the cells treated with the free drugs, single-drug–loaded nanoparticles, or non-biotin–decorated nanoparticles. BNDQ exhibited clear inhibition of both the activity and expression of P-glycoprotein in MCF-7/ADR cells. More importantly, it caused a significant reduction in doxorubicin resistance in MCF-7/ADR breast cancer cells both in vitro and in vivo , among all the groups. Overall, this study suggests that BNDQ has a potential role in the treatment of drug-resistant breast cancer.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Zhiwen Zhang,Zeying Liu,Li Ma,Shijun Jiang,Yixin Wang,Haijun Yu,Qi Yin,Jingbin Cui,Yaping Li
Multidrug resistance (MDR) remains one of the major challenges for successful chemotherapy. Herein, we tried to develope a mitochondria targeted teniposide loaded self-assembled nanocarrier based on stearylamine (SA-TSN) to reverse MDR of breast cancer. SA-TSN was nanometer-sized spherical particles (31.59 ± 3.43 nm) with a high encapsulation efficiency (99.25 ± 0.21%). The MDR in MCF-7/ADR cells was obviously reduced by SA-TSN, which mainly attributed to the markedly reduced expression of P-gp, increased percentages in G2 phase, selectively accumulation in mitochondria, decrease of mitochondrial membrane potential, and greatly improved apoptosis. The plasma concentration of teniposide was greatly improved by SA-TSN, and the intravenously administered SA-TSN could accumulate in the tumor site and penetrate into the inner site of tumor in MCF-7/ADR induced xenografts. In particular, the in vivo tumor inhibitory efficacy of SA-TSN in MCF-7/ADR induced models was more effective than that of teniposide loaded self-assembled nanocarrier without stearylamine (TSN) and teniposide solution (TS), which verified the effectiveness of SA-TSN in reversal of MDR. Thereby, SA-TSN has potential to circumvent the MDR for the chemotherapy of breast cancer.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Microfluidics and Nanofluidics
·
2014
·Vol. 17
·期 5
·831-842
·
IF 2.665
Sun Duanping,Lu Jing,Chen Zuanguang,Yu Yanyan,Li Yinbao
The formation of three-dimensional (3D) multicellular cell spheroids such as microspheres and embryoid bodies has recently gained much attention as a useful cell culture technique, but few studies have investigated the suitability of glass for spheroids formation and culture. In this work, we present a novel three-dimensional microfluidic device made of poly(dimethylsiloxane) (PDMS) and glass for the easy and rapid synthesis and culture of tumor spheroid. The cell culture unit is composed of an array of microwells on the bottom of a glass plate, bigger microwells and elastomeric microchannels on the top of a PDMS plate. Cell suspension can be easily introduced into the cell culture unit and exchange with the external liquid environment by the microfluidic channels. A single tumor spheroid can be formed and cultured in each glass cell culture chamber, the surface of which was modified with poly(vinyl alcohol) to render it to be resistant to cell adhesion. As the cell culture medium could be replaced, spheroids of the human breast cancer (MCF-7) cells were cultured on the chip for 3 days, reaching the diameters of about 150 μm. Furthermore, the MCF-7 cells were successfully cultured on the chip in 2D and 3D culture modes. Results have shown that glass is well suitable for multicellular tumor spheroids culture. The established platform provides a convenient and rapid method for tumor spheroid culture, which is also adaptable for anticancer drug screening and fundamental biomedical research in cell biology.
研究领域:
生物医学工程
·
癌症研究
·
细胞生物学
·
微流控技术
✓ 已验证
产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2016
·Vol. 183
·期 9
·2605-2613
·
IF 4.831
Liu Yanting,Zhou Shixin,Fan Louzhen,Fan Hong
We have prepared graphene quantum dot-europium(III) complex composites by noncovalently connecting chelating ligands dibenzoylmethane (DBM) and 1,10-phenanthroline (Phen) with graphene quantum dots (GQDs) first, followed by coordination to Eu(III). The resulting composites are well water-soluble and display red fluorescence of high color purity. The composites were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray diffraction. Aqueous solutions of the composites under 365 nm excitation display fluorescence with a peak at 613 nm and a quantum yield as high as 15.5 %. The good water solubility and stable photoluminescence make the composites very different from other Eu(III)-based coordination complexes. The composites are cell viable and can be used to label both the cell membrane and the cytoplasm of MCF-7 cells. They are also shown to act as bioprobes for in-vivo localization of tumorous tissue. In our perception, such composites are expected to possess wide scope because of the many functionalizations that are possible with GQDs.
Synthesis of red fluorescent graphene quantum dot-europium complex composites for use in bioimaging.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
分析化学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）