MOLECULES
·
2024
·Vol. 29
·期 18
·4375
·
IF 4.2
Ran Luo,Haoyi Zhao,Siqi Deng,Jiale Wu,Haijun Wang,Xiaoshan Guo,Cuicui Han,Wenkang Ren,Yinglong Han,Jianwen Zhou,Yu Lin,Ming Bu
In this study, novel ergosterol peroxide (EP) derivatives were synthesized and evaluated to assess their antiproliferative activity against four human cancer cell lines (A549, HepG2, MCF-7, and MDA-MB-231). Compound3gexhibited the most potent antiproliferative activity, with an IC50value of 3.20 µM against MDA-MB-231. This value was 5.4-fold higher than that of the parental EP. Bioassay optimization further identified3gas a novel glutaminase 1 (GLS1) inhibitor (IC50= 3.77 µM). In MDA-MB-231 cells,3greduced the cellular glutamate levels by blocking the glutamine hydrolysis pathway, which triggered reactive oxygen species production and induced caspase-dependent apoptosis. Molecular docking indicated that3ginteracts with the reaction site of the variable binding pocket by forming multiple interactions with GLS1. In a mouse model of breast cancer,3gshowed remarkable therapeutic effects at a dose of 50 mg/kg, with no apparent toxicity. Based on these results,3gcould be further evaluated as a novel GLS1 inhibitor for triple-negative breast cancer (TNBC) therapy.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 14
·6334-6347
·
IF 5.396
Bei Li,Xiaodong Wang,Shasha Hong,Qi Wang,Lin Li,Omer Eltayeb,Chuan Dong,Shaomin Shuang
Herein, PPy@MnO2 nanocomposites were first harvested by anchoring MnO2 nanosheets on polypyrrole (PPy) nanoparticles via an in situ redox reaction, then polyethylene glycol (PEG) modifier and methylene blue (MB) photosensitizer were linked through electrostatic interactions to obtain PPy@MnO2-PEG-MB nanoarchitectures. PPy nanoparticles ensure photothermal therapy (PTT) ability and MnO2 nanosheets ameliorate tumor hypoxia for enhanced photodynamic therapy (PDT). Therefore, a multifunctional nanotherapeutic system was constructed for the combined PTT/PDT of tumors. For extracellular photothermal properties, the optimal temperature elevation was 52.6 °C with 54.4% photothermal conversion efficiency. The extracellular PDT ability was measured by detecting 1O2 generation; more 1O2 was produced under acidic conditions in the presence of H2O2 (a simulated tumor microenvironment). The effective cellular uptake of the nanotherapeutic system in HeLa cells was observed by confocal laser scanning microscopy (CLSM). CLSM also indicated that more 1O2 was generated by the nanotherapeutic system as compared to free MB in HeLa cells, confirming the amelioration of tumor hypoxia by MnO2 nanosheets. MTT assays demonstrated that the nanotherapeutic system possessed superior biocompatibility without laser irradiation, and the lowest cell viabilities for single PTT and PDT groups were 13.78%, 38.82% respectively, while there was only 1.29% cell viability in the combined PTT and PDT group. These results suggest that the strategy of assembling PPy with MnO2 for a multifunctional PTT and enhanced PDT nanoplatform was realized, and opens up an unimpeded approach for integrating photothermal reduction materials with MnO2 for use in synergistic PTT and PDT.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2024
·
IF 2.8
Linqian Chen,Meifeng Chen,Yan Xie,Yuyan Zhang,Shutian Mo,Yongfei He,Tianyi Liang,Yuan Liao,Renbin Huang,Guodong Huang,Chuangye Han,Thi Thai Hoa Pham
Several studies have suggested a potential antitumor effect of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD). To further understand the mechanism of action of this compound, we investigated its effect on the phosphatidylinositol-3-kinase (PI3K)/serine–threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. We show that DMDD application significantly inhibited the proliferation of breast cancer cell lines MDA-MB-231 and ER-α positive MCF-7. Furthermore, DMDD application resulted in increased intracellular reactive oxygen species (ROS) levels, apoptosis and autophagy, whereas it downregulated the expression of PI3K, Akt and mTOR mRNA and proteins, and increased the expression of LC3II/I and p62 proteins. In a mouse breast cancer xenograft model, DMDD inhibited tumor growth. Expression analyses suggest that ROS levels were higher in DMDD treated tumor tissues, whereas immunohistochemical analyses suggest that apoptotic cells were more prevalent in the DMDD treated group compared to the control group. Taken together, our results suggest that the molecular mechanism of action of DMDD may involve the enhancement of breast cancer autophagy through the PI3K/Akt/mTOR signaling pathway by mediating ROS expression.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Xiaohong Xu,Vinothakumar Rajamanicham,Sujing Xu,Zhoudi Liu,Tao Yan,Guang Liang,Guilong Guo,Huiping Zhou,Yi Wang
Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking prognostic and effective therapeutic targets currently. In this study, we evaluated the toxic potential of schisandrin A (SchA), a bioactive phytochemical found in Schisandra chinensis in TNBC. The anti-cancer effect and underlying mechanism of SchA on MDA-MB-231 and BT-549 cells were determined in vitro and in xenograft mouse model. Our data show that SchA markedly inhibited the growth of TNBC cells via induction of cell cycle arrest and cell apoptosis. Moreover, over activation of Wnt signaling was observed in TNBC cells, which was significantly suppressed by the treatment of SchA. Also, SchA treatment activated ER stress in TNBC cells. Finally, we verified these inhibitory effects of SchA in the MDA-MB-231 xenograft mouse model. In conclusion, SchA effectively inhibited TNBC in preclinical models by inducing cell cycle arrest and apoptosis via regulating Wnt/ER stress signaling pathway. All of these data indicate that SchA could be a potential candidate for the treatment of TNBC.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2019
·Vol. 144
·期 22
·6533-6540
·
IF 4.019
Ziyi Cheng,Rui Wang,Yanlong Xing,Linlu Zhao,Jaebum Choo,Fabiao Yu
Cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) are important diagnostic biomarkers for acute myocardial infarction (AMI). Many efforts have been undertaken to develop highly sensitive detection methods for the quantitative analysis of these dual targets. However, current immunoassay methods are inadequate for accurate measurement of cTnI and CK-MB, due to their limited detection sensitivity. Thus, there is still an urgent demand for a new technique that will enable ultrahigh sensitive detection of these biomarkers. In this study, we developed a surface-enhanced Raman scattering (SERS)-based sandwich immunoassay platform for the ultrasensitive detection of cTnI and CK-MB. In this study, a monoclonal-antibody-immobilized gold-patterned chip was used as a SERS active template. Target samples and polyclonal-antibody-conjugated Au@Ag core–shell nanoparticles were then added. Using this SERS platform, the concentration of biomarkers could be quantified by monitoring the characteristic Raman peak intensity of Raman reporter molecules. Under optimized conditions, the limits of detection (LODs) were estimated to be 8.9 pg mL−1 and 9.7 pg mL−1 for cTnI and CK-MB, respectively. Thus, the proposed SERS-based immunoassay has great potential to be an effective diagnostic tool for the rapid and accurate detection of cTnI and CK-MB.
研究领域:
分析化学
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生物医学工程
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心脏病学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 6
·1223-1234
·
IF 5.047
Huiru Li,Xinyue Zhang,Xilin Lin,Shuqiang Zhuang,Yan Wu,Zhong Liu,Jianhua Rong,Jianhao Zhao
Based on the concept of starving tumor therapy, in this study we put forward a new idea that the pH-sensitive Ca2+ delivery of calcium carbonate nanoparticles (CaCO3 NPs) induced blood coagulation of tumor vessels, and first explored the effect of CaCO3 NPs on the in vitro and in vivo blood coagulation by acid stimulus. CaCO3 NPs with a size of about 100 nm and a porous structure of several nanometers were synthesized in an emulsion system, which showed a high loading capacity (49%) of doxorubicin hydrochloride (DOX) with an encapsulation efficiency of 98% and a pH-sensitive drug delivery. The hemolysis test showed that CaCO3 NPs were blood compatible. The in vitro Ca2+ delivery and blood clotting tests indicated that CaCO3 NPs pH-sensitively released Ca2+, and caused rapid blood coagulation at pH 5.0 but no thrombus at pH 7.4. Confocal laser scanning microscopy showed that after uptake by MCF-7 or MDA-MB-231 breast cancer cells, CaCO3 NPs mainly distributed in endosomes/lysosomes within the initial 2 h and then decomposed by acid stimulus, leading to the intracellular delivery of Ca2+ that subsequently migrated outside the cells. CaCO3 NPs were nontoxic to NIH3T3 mouse fibroblasts, but highly toxic to both MCF-7 and MDA-MB-231 cells after loading DOX. After topical administration into the breast tumors of mice, CaCO3 NPs evoked significant thrombosis and hemorrhage of tumor vasculature by hematoxylin–eosin and Masson's trichrome staining. These results indicated that CaCO3 NPs could induce blood coagulation via acid stimulus, showing potential applications in blocking tumor vessels for starving tumor therapy.
研究领域:
纳米技术
·
癌症治疗
·
药学科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2024
·
IF 2.6
Yaling Yuan,Yue Zhong,Yanbin Yang,Ke Li
Myoglobin (Myo), creatine kinase-MB (CKMB), and cardiac troponin I (cTnI) are crucial biomarkers for diagnosing acute myocardial infarction (AMI) The accurate and rapid detection of these three targets can greatly improve the prognosis of AMI patients. Herein, this study developed a microfluidic immunofluorescence method that can detect all three targets in 10–15 min. Ultrasonic atomization and spray technology are used to modify the surface of the injection-molded microfluidic chip (MFC), which effectively solves the problem of biological cross-linking and antibody immobilization on the MFC surface. In addition, it improves the hydrophilicity of the chip surface, thus enhancing fluid self-driving effect. The linear response towards Myo, CKMB and cTnI range from 5 ng/mL to 500 ng/mL, 1 ng/mL to 70 ng/mL, and 0.05 ng/mL to 30 ng/mL, respectively. The intra-batch precision is ≤ 10%, and the inter-batch precision is ≤ 15%. Furthermore, this method shows good consistency compared with the BECKMAN ACCESS2 chemiluminescent immunoanalyzer. The present work provides an AMI diagnostic method with high sensitivity, good repeatability, high accuracy and simple operation, which can satisfy the needs of clinical diagnosis, and shows promising application prospects.
研究领域:
生物医学工程
·
心脏病学
·
诊断方法
·
微流控技术
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-8
·
IF 3.998
Tan Xiao-Hui,Li Yu-Bin,Liao Yan,Liu Hua-Zhong
In this work, an enzyme-free fluorescence resonance energy transfer (FRET) strategy was established for rapid and specific detection of the DNA sequence from Vibrio parahaemolyticus (VP) using hybridization chain reaction (HCR) amplification and triplex DNA. The triplex forming oligonucleotide (TFO) was labelled with carboxyfluorescein (FAM) as fluorescence donor, and hairpin sequence H1 was labelled by tetramethylrhodamine (TAMRA) as fluorescence receptor. In the present target VP DNA, the hairpin structure of molecular beacon (MB) was opened, the free end was released and hybridized with H1-TAMRA, and the HCR reaction was triggered by the alternate supplementation of H1-TAMRA and H2 to produce the notch double helix analogue. After the addition of TFO-FAM, a triplex structure was formed between HCR products (H1-TAMRA/H2) and TFO-FAM. A close contact between the donor and the receptor resulted in FRET. Under the optimal conditions, the fluorescence quenching value was inversely proportional to the concentration of target VP DNA in the range of 0.1–50 nmol L −1 , and the detection limit was 35 pmol L −1 .
研究领域:
生物化学
·
分子生物学
·
分析化学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2015
·Vol. 4
·期 3
·412-417
·
IF 3.831
Chao Chen,Pan Zheng,Ziyang Cao,Yinchu Ma,Jie Li,Haisheng Qian,Wei Tao,Xianzhu Yang
Redox-responsive polymers exhibit great potential as drug delivery systems. Herein, a redox-responsive PEGylated hyperbranched polyphosphoester (PPE) was synthesized through (A2 + B3) type polycondensation. The obtained hyperbranched PPE can self-assemble into nanoparticles in water. The biocompatibility of the nanoparticles was evaluated. The hydrophobic chemotherapy drug doxorubicin (DOX) can be efficiently encapsulated into the obtained nanoparticles. Such DOX-loaded nanoparticles exhibited excellent stability due to the PEGylation, and showed redox-responsive drug release behavior. In addition, flow cytometric analyses demonstrated that the redox-responsive nanoparticles could be efficiently internalized into the human breast cancer cell line MDA-MB-231, and intracellular glutathione enhanced the intracellular drug release from the redox-responsive hyperbranched PPE based nanoparticles. Therefore, such nanoparticles resulted in the enhanced inhibition of tumor cell growth, suggesting the potential of redox-responsive PEGylated hyperbranched PPE in anticancer drug delivery.
研究领域:
药剂学
·
材料科学
·
肿瘤学
·
聚合物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2023
·
IF 5.5
Chen Dong,Luo Xuan,Xi Fengna
Sensitive detection of tumor biomarkers is crucial for early diagnosis and prognosis evaluation of cancer. Owing to no need of labelled antibody, formation of sandwich immunocomplexes and additional solution-based probe, probe-integrated electrochemical immunosensor for reagentless detection of tumor biomarkers is highly desirable. In this work, sensitive and reagentless detection of a tumor biomarker is realized based on fabrication of a probe-integrated immunosensor by confining redox probe in electrostatic nanocage array modified electrode. Indium tin oxide (ITO) electrode is employed as the supporting electrode because it is cheap and easily available. The silica nanochannel array consisted of two layers with opposite charges or different pore diameters was designated as bipolar films (bp-SNA). In this work, Electrostatic nanocage array is equipped on ITO electrode by growth of bp-SNA with two layered nanochannel array having different charge properties including a negatively charged silica nanochannel array (n-SNA) and a positively charged amino-modified SNA (p-SNA). Each SNA can be easily grown with 15 s using electrochemical assisted self-assembly method (EASA). Methylene blue (MB) is applied as the model electrochemical probe with positive charge to be confined in electrostatic nanocage array with stirring. The combination of the electrostatic attraction from n-SNA and the electrostatic repulsion from p-SNA endows MB with highly stable electrochemical signal during continuous scanning. When the amino groups of p-SNA are modified using the bifunctional glutaraldehyde (GA) to introduce aldehydes, the recognitive antibody (Ab) of the most commonly used tumor biomarker, carcinoembryonic antigen (CEA), can be covalently immobilized. After the non-specific sites are blocked, the immunosensor is successfully fabricated. As the formation of antigen-antibody complex decreases electrochemical signal, the immunosensor can achieve reagentless detection of CEA ranged from 10 pg/mL to 100 ng/mL with a low limit of detection (LOD, 4 pg/mL). Determination of CEA in human serum samples is realized with high accuracy.
研究领域:
生物医学工程
·
分析化学
·
癌症诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2023
·
IF 6.7
Jie Dai,Zhiyi Peng,Shuwei Shen,Binbin Huang,Lili Ren,Jia Liu,Chia Hung Chen,Guoguang Chen
The dysfunction of intracellular proteins is frequently associated with various diseases, such as cancer. The exogenous proteins in cells are usually assembled with specific configurations due to physiological confinement/crowding to exhibit novel features in protein structure, folding or conformational stability, distinguished with their behaviors in buffer solutions. Here, we synthesized exogenous proteins in a confined/crowded condition, to explore protein activity within the cells. The findings suggested that the confinement and crowding effects on protein activity are heterogeneous; they showed an inhibitory consequence on HRP by decreasing Km (from ~9.5- and ~21.7-fold) and Vmax (from ~6.8- and ~20.2-fold) lower than that of dilute solutions. Interestingly, the consequences on Cyt C seem more complicated, and the crowding exerts a positive effect by increasing Km ~3.6-fold and Vmax ~1.5-fold higher than that of dilute solutions; however, the confinement takes a negative consequence by decreasing Km ~2.0 and Vmax ~8.3 times. Additionally, in contrast to traditional nanoparticles-based confinement models, we synthesized a biodegradable nanoparticle to mimic the confined space, and the biggest advantage of this novel model is that the particles can be degraded and thus it can provide more intuitive observations of the target protein properties under the confinement and after release. Furthermore, we also evaluated protein activity in different cellular environments, indicating the exogenous protein activity was closely related to the crowdedness of cellular environments, and the inhibition of protein activity in MDA-MB-231 cancer cells was more obvious than HEK293 normal cells. Finally, SAXS analysis revealed the correlation between the protein conformation and the different environments. Our work will provide a unique way for precisely assessing whether the target cellular environments are native matrix in which specific exogenous protein drugs delivered to function or whether they display a therapeutic role, which is of great significance for screening and development of new drugs.
研究领域:
生物物理学
·
细胞生物学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Hui Zhang,Qingwen Xue,Zihan Zhou,Ningning He,Shangyong Li,Cheng Zhao
Breast cancer (BC) is the most common malignancy in women worldwide, and the standard treatment is chemotherapy or radiotherapy after surgery. In order to reduce the side effects of chemotherapy, various nanoparticles (NPs) have been discovered and synthesized, which has become a promising treatment for BC. In this study, a co-delivery nanodelivery drug system (Co-NDDS) was designed and synthesized with 2,3-dimercaptosuccinic acid (DMSA) coated Fe 3 O 4 NPs as core encapsulated into chitosan/alginate nanoparticles (CANPs) shell, doxorubicin (DOX) and hydroxychloroquine (HCQ) as loading drugs. Smaller NPs carrying DOX (FeAC-DOX NPs) were loaded into larger NPs containing HCQ (FeAC-DOX@PC-HCQ NPs) by ionic gelation and emulsifying solvent volatilization methods. The physicochemical properties of this Co-NDDS were characterised, followed by in vitro studies of the anticancer effects and mechanisms using two different BC cell lines, MCF-7 cells and MDA-MB-231 cells. The results indicated that the Co-NDDS showcases exemplary physicochemical qualities and encapsulation capacity, facilitating accurate intracellular release through pH-sensitive attributes. Importantly, NPs can significantly increase the in vitro cytotoxicity of co-administered drugs and effectively inhibit the autophagy level of tumour cells. The Co-NDDS constructed in this study provides a promising strategy for the treatment of BC.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 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）