Frontiers in Chemistry
·
2024
·
IF 3.8
Xu Xuemei,Zhu Zhaojingtao,Chen Siyu,Fu Yanneng,Zhang Jinxia,Guo Yangyang,Xu Zhouyang,Xi Yingying,Wang Xuebao,Ye Faqing,Chen Huijun,Yang Xiaojiao
Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks.Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers.Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 μM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties.Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study’s mechanistic exploration, highlighting B7’s simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.
研究领域:
药理学
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肿瘤学
·
药物化学
·
细胞生物学
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炎症
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2019
·Vol. 54
·期 16
·11243-11253
·
IF 3.442
Rao Chaohui,Guo Xia,Li Min,Sun Xiaoqing,Lian Xiaojie,Wang Huifang,Gao Xianghua,Niu Baolong,Li Wenfeng
The development of high drug loading and sustained release nanoparticles by simple and economical methods is significant for the treatment of diseases. Amorphous calcium carbonate (ACC) is an ideal drug delivery system because of its excellent pH responsiveness, biocompatibility and biodegradability. In this work, ACC nanoparticles were successfully precipitated in ethanol–calcium solutions using ammonium carbonate as the internal source of CO 2 , which exhibited a relatively narrow size distribution in range of 10–200 nm. The microscopic morphology, amorphous characters, porous structure and thermal behavior of resultants were investigated by electron microscopy, Fourier-transform infrared spectroscopy, Brunauer–Emmett–Teller and thermogravimetric analysis, respectively. In vitro drug release assay showed that ACC nanoparticles had high loading capacity of curcumin (Cur) and favorable drug release properties. Furthermore, ACC-Cur showed excellent abilities to scavenge free radicals, protect Cur stability and damage A549 cells, providing a broadened space for the applications of this material in the fields of biomedical or food.
研究领域:
纳米技术
·
药剂学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
BMC CANCER
·
2019
·Vol. 19
·期 1
·1-9
·
IF 2.933
Xiao Hui,He Mudan,Xie Guogang,Liu Yanan,Zhao Yuxia,Ye Xiong,Li Xingjing,Zhang Min
Background Cancer cells release exosomes and can be taken up by mast cells (MCs), but the potential functional effects of MCs on tumor metastasis remain unknown.MethodExosomes were isolated from the lung adenocarcinoma cell line A549, and the uptake of PKH26-labeled exosomes by bone marrow MCs was examined via flow cytometry and fluorescence microscopy. Cytokines and tryptase in MC supernatant were analyzed using an ELISA kit, and the presence of tryptase was evaluated by Western blotting. Cell proliferation and migration were determined through CCK-8 and transwell assays. Proteins in the tryptase-JAK-STAT signaling pathway were detected by Western blotting.Results In this study, we show that exosomes from A549 cells can be taken up by MCs. Moreover, A549 exosomes contain stem cell factor (SCF) to MCs and subsequently induce the activation of MCs through SCF-KIT signal transduction, which leads to MC degranulation and the release of tryptase. Tryptase accelerates the proliferation and migration of human umbilical vein endothelial cells (HUVECs) through the JAK-STAT signaling pathway.Conclusion sOur results reveal a mechanism for metastasis in which exosomes can transfer SCF to and activate MCs, which can affect the release of tryptase and the angiogenesis of HUVECs.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2014
·
IF 3.552
Wenjing Zhang,Zhengwei Mao,Changyou Gao
Thermo-sensitive microgel particles may exert a swelling force inside cells and influence on cell viability due to their volume transition in response to external temperature change. In this study, cross-linked poly(N-isopropylacrylamide) (PNIPAM) microgel particles with a thermo-responsive volume expansion ability were prepared by precipitation polymerization of NIPAM, poly(ethylene glycol) diacrylate and acrylic acid. To endow the microgel particles with enhanced cellular uptake and visualization, cell penetrating peptide TAT and fluorescent probe were further covalently immobilized. The cellular uptake, intracellular distribution and thermo-responsive cytotoxicity of the microgel particles were studied by co-culture with lung adenocarcinoma (A549) cells. The PNIAPM microgel particles were largely ingested by A549 cells and mainly located in lysosomes. TAT modification enhanced the cellular internalization of particles but did not alter their intracellular distribution. While the PNIPAM microgel particles did not show significant impact on cell viability at 37 °C, they caused cytotoxicity to some extent when being cultured at 25 °C for 4 h. Doxorubicin loaded PNIPAM microgel particles showed the strongest cytotoxicity when being cultured at 25 °C for 4 h, suggesting the combinational effect of intracellular volume expansion and drug release on cells.
研究领域:
材料科学
·
生物医学工程
·
药学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Lanmei Chen,Guodong Li,Fa Peng,Xinming Jie,Guangzhi Dongye,Kangrong Cai,Ruibing Feng,Baojun Li,Qingwang Zeng,Kaiyi Lun,Jincan Chen,Bilian Xu
In the present study, it was found that the ruthenium (II) imidazole complex [Ru(Im) 4 (dppz)] 2+ (Ru1) could induce significant growth inhibition and apoptosis in A549 and NCI-H460 cells. Apart from the induction of apoptosis, it was reported for the first time that Ru1 induced an autophagic response in A549 and NCI-H460 cells as evidenced by the formation of autophagosomes, acidic vesicular organelles (AVOs), and the up-regulation of LC3-II. Furthermore, scavenging of reactive oxygen species (ROS) by antioxidant NAC or Tiron inhibited the release of cytochrome c , caspase-3 activity, and eventually rescued cancer cells from Ru1-mediated apoptosis, suggesting that Ru1 inducing apoptosis was partially caspase 3-dependent by triggering ROS-mediated mitochondrial dysfunction in A549 and NCI-H460 cells. Further study indicated that the extracellular signal-regulated kinase (ERK) signaling pathway was involved in Ru1-induced autophagy in A549 and NCI-H460 cells. Moreover, blocking autophagy using pharmacological inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) enhanced Ru1-induced apoptosis, indicating the cytoprotective role of autophagy in Ru1-treated A549 and NCI-H460 cells. Finally, the in vivo mice bearing A549 xenografts, Ru1 dosed at 10 or 20 mg/kg significantly inhibited tumor growth.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Ziqi Yan,Qiong Shi,Xumei Liu,Jinhua Li,Vidhula Ahire,Shenqiu Zhang,Jing Zhang,Dun Yang,Thaddeus D. Allen
Plants are a rich source for bioactive compounds. However, plant extracts can harbor a mixture of bioactive molecules that promote divergent phenotypes and potentially have confounding effects in bioassays. Even with further purification and identification, target deconvolution can be challenging. Corynoline and acetylcorynoline, are phytochemicals that were previously isolated through a screen for compounds able to induce mitotic arrest and polyploidy in oncogene expressing retinal pigment epithelial (RPE) cells. Here, we shed light on the mechanism by which these phytochemicals can attack human cancer cells. Mitotic arrest was coincident to the induction of centrosome amplification and declustering, causing multi-polar spindle formation. Corynoline was demonstrated to have true centrosome declustering activity in a model where A549 cells were chemically induced to have more than a regular complement of centrosomes. Corynoline could inhibit the centrosome clustering required for pseudo-bipolar spindle formation in these cells. The activity of AURKB, but not AURKA or polo-like kinase 4, was diminished by corynoline. It only partially inhibited AURKB, so it may be a partial antagonist or corynoline may work upstream on an unknown regulator of AURKB activity or localization. Nonetheless, corynoline and acetylcorynoline inhibited the viability of a variety of human cancer derived cell lines. These phytochemicals could serve as prototypes for a next-generation analog with improved potency, selectivity or in vivo bioavailability. Such an analog could be useful as a non-toxic component of combination therapies where inhibiting the chromosomal passenger protein complex is desired.
研究领域:
药理学
·
癌症生物学
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细胞生物学
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植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2024
·Vol. 19
·期 9
·e0310253
·
IF 2.9
Zhaolei Wang,Haixia Du,Haofang Wan,Jiehong Yang,Haitong Wan
Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that can cause severe bacterial pneumonia. Amygdalin is the main active pharmaceutical ingredient of bitter almond, which has broad-spectrum antibacterial, anti-inflammatory, anti-oxidation and immunomodulatory effects. It is also the main ingredient of Yinhua Pinggan granule, which is commonly used to moisten the lung and relieve cough. However, little is known about the effects of amygdalin on MRSA. In this study, we found that amygdalin exhibited good antimicrobial activity in vitro against MRSA. Amygdalin has a protective effect on MRSA infected cells, and the effect is better when combined with levofloxacin. It also can reduce the adhesion and invasion of MRSA to cells. Amygdalin has anti-inflammatory and antioxidant effects, which can significantly reduce the increase of inflammatory factors and the production of ROS caused by infection. The protective mechanism of amygdalin on cells may be related to inhibiting the expression of NLRP3, ASC and IL-1β pyroptosis pathways. Taken together, our study suggests that amygdalin exerts antibacterial effects by affecting biofilm formation, the expression of virulence factors, and drug resistance genes. Amygdalin combined with levofloxacin has a protective effect on A549 cells infected with MRSA, and the mechanism may be related to the inhibition of inflammatory response, oxidative damage and pyroptosis.
研究领域:
药理学
·
微生物学
·
传染病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemistrySelect
·
2024
·Vol. 9
·期 5
·e202304100
·
IF 1.9
Lu Gan,Yuxuan Li,Yongzhi Xia,Jing Yang,Yan Chen
Graphical Herein, we constructed a novel carbon nitride compound called PTCNx, featuring a large π-conjugated skeleton, and employed it as a carrier for delivering aromatic clinical drugs for the first time. PTCN 550 achieving an unprecedented 99 % loading efficacy of DOX and resulting PTCN 550 -DOX demonstrated effective anti-tumor activity for CNE-2Z tumor cells. π-π interactions, serving as a pivotal driving force, hold enduring significance in the realm of drug delivery system development, primarily due to the prevalence of aromatic moieties in a substantial number of clinically relevant pharmaceutical compounds. Herein, we constructed a novel carbon nitride compound called PTCNx, featuring a large π-conjugated skeleton, and employed it as a carrier for delivering aromatic clinical drugs for the first time. We conducted sequence characterization of their chemical structure, optical properties, and morphology, along with extensive research to analyze their significant enhancement in drug loading capacity. Of particular note was the exceptional loading efficiency of Doxorubicin (DOX) under alkaline conditions, achieving an unexpected 99 % efficacy, significantly surpassing the capabilities of traditional carbon nitrides with limited π-conjugated systems. Cell tests illustrated that PTCN 550 carrier exhibited favorable biocompatibility and low toxicity for normal and tumor cells, showing its potential as a drug carrier. However, PTCN 550 -DOX complex effectively inhibited both A549 and CNE-2Z tumor cells. And it demonstrated more effective anti-tumor activity for CNE-2Z than for A549 cells. This study marks a significant milestone, representing the inaugural endeavor to elucidate the improvement in loading capacity through the strategic extension of the π-conjugated system design paradigm.
研究领域:
药学
·
材料科学
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2016
·Vol. 16
·期 6
·5569-5576
·
IF 1.338
Li Qinqin,Li Chenglin,Tong Weijun
Here, a novel poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for magnetic resonance (MR) and fluorescence imaging was developed for cell imaging. PLGA NPs loaded with fluorescent dye Nile red (NR) and surface-coated with poly(ethyleneimine) (PEI) were produced in a single
step nanoprecipitation process. Diethylenetriamine pentaacetic dianhydride (DTPA) was conjugated to PLGA/NR@PEI NPs through amidation reaction between –COOH of DTPA and –NH2 of PEI, which can chelate gadolinium (Gd3+) as an MR imaging contrast agent. The PLGA/NR@PEI-DTPA-Gd
NPs exhibited a uniform particle size of ∼200 nm and were stable in culture medium. These NPs had a high T
1 relaxivity (R
1) of 28.36 mM−1S−1. They did not introduce serious cytotoxicity against A549 lung cancer cells.
Furthermore, fluorescence and MR imaging studies on A549 lung cancer cells in vitro revealed that PLGA/NR@PEI-DTPA-Gd NPs can serve as an efficient fluorescence/MR dual-modality imaging nanoprobe.
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
医学成像
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Like Ning,Chaoqun You,Yu Zhang,Xun Li,Fei Wang
Hydrogel for various applications, such as cell encapsulation and controlled release of drugs, has attracted the field of biomaterials in the past decades. Specially, research on the surface-modified nanocellulose hydrogel has grown rapidly on account of the importance of target delivery in the anti-cancer therapy. In this work, surface-modified nanocellulose was mixed with hexadecyl amine as long chains to blend to build a network to produce hydrogel, which was successfully developed for controlled and targeted delivery of paclitaxel. The pH-stimuli surface-modified nanocellulose hydrogel was characterized and biological evaluated in vitro. The hydrogel was stable at pH 7.4 and paclitaxel was released by the shape change of hydrogel in an acidic environment (pH 5.5), and the sustained release of paclitaxel was observed at pH 5.5. The vitro cytotoxicity studies indicated that the drug accumulation and the inhibition of A549 and HepG2 cells was effectively increased by the surface-modified nanocellulose hydrogel as compared with free paclitaxel. The inhibitory effect of A549 cells was improved by nearly 30% as compared with free paclitaxel and the apoptosis rate was up to 90.5% after 12 h incubation. In addition, the inversion test and the results of a series of cell experiments in vitro demonstrated a good performance of the surface-modified nanocellulose hydrogel.
研究领域:
生物材料
·
药剂学
·
癌症研究
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Xinyu Hu,Yongmei Wang,Liangliang Zhang,Man Xu,Jianfa Zhang,Wei Dong
Salecan is a novel water-soluble extracellular β-glucan and suitable for the hydrogel preparation due to its excellent physicochemical and biological properties. The present article describes the fabrication and characterization of a pH/magnetic field-driven hydrogel based on salecan-g-poly(vinylacetic acid-co-2-hydroxyethyl acrylate) [poly(VA-co-HEA)] copolymer and Fe 3 O 4 @Agarose nanoparticles for drug release testing. Vibrating sample magnetometer characterization verified that integration of Fe 3 O 4 @Agarose nanoparticles in the copolymer provided the sensitivity to magnetic fields. The doxorubicin hydrochloride (DOX) release test showed a pH/magnetic field-triggered and sustained release property, and the release could be accelerated under mildly acidic conditions or the presence of an external magnetic field. Meanwhile, the increase in salecan content could also enhance the release rate. Cytotoxicity assays revealed that the released DOX maintained relatively high killing efficacy of A549 cells. In sum, these salecan-g-poly(VA-co-HEA)/Fe 3 O 4 @Agarose hydrogels were well-suited for magnetically targeted drug delivery systems.
研究领域:
药学
·
材料科学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 28
·6128-6138
·
IF 5.344
Ruihong Xie,Peng Yang,Shaojun Peng,Yongbin Cao,Xianxian Yao,Shengdi Guo,Wuli Yang
In recent years, zeolitic imidazolate framework-8 (ZIF-8) has become an attractive metal organic framework (MOF) material in drug delivery for cancer chemotherapy. However, as a drug delivery system, ZIF-8 still shows some disadvantages, such as short blood circulation time and poor tumor targeting, leading to reduced drug delivery efficiency and unsatisfactory treatment. Herein, we developed a phosphorylcholine-based zwitterionic copolymer coated ZIF-8 nanodrug (DOX@ZIF-8@P(MPC-co-C7A)), and the obtained nanodrug was prepared via a charge-conversional zwitterionic copolymer coating on DOX@ZIF-8 composites. In this system, DOX was encapsulated in the framework of ZIF-8, which could reduce the drug leakage in the bloodstream. The phosphorylcholine-based zwitterionic copolymer effectively extended the blood circulation time, resulting in enhanced tumor accumulation of the nanodrug. Once the nanodrug reached the tumor site, the surface charge of the system could rapidly convert to positive, resulting in an enhanced tumor cellular uptake. Finally, in the acidic environment inside intracellular organelles, DOX will be released rapidly for chemotherapy owing to the fast disintegration of ZIF-8 frameworks. Therefore, the obtained nanodrug could effectively inhibit the growth of A549-bearing tumors (93.2% tumor inhibition rate) with negligible side effects. Overall, this work significantly improved the drug delivery efficiency of ZIF-8, which may pave the way for the biomedical applications of ZIF-8 crystals in anti-tumor drug delivery.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
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）