Cancer Cell International
·
2020
·Vol. 20
·期 1
·1-16
·
IF 4.175
Zhang Qing,Wu Lian,Liu Shaozheng,Chen Qingjie,Zeng Lingpeng,Chen Xuezhong,Zhang Qing
Background To investigate the efficacy of a PLGA-based nanobody complex in photodynamic therapy (PDT) and NIR-II imaging in A549 tumor hypoxic model.MethodIR1048-MZ was firstly synthesized by conjugating a nitro imidazole group to IR1048. IR1048-MZ and Cat were then encapsulated in PLGA-SH solution. Anti-EGFR-Nanobody was also expressed and purified, and finally Anti-EGFR-Nanobody@PLGA-IR1048MZ-Cat (Nb@IC-NPs) nanobody complex was obtained based on the formation of desulfide bond between PLGA-SH and Anti-EGFR-Nanobody. Size distribution and morphology were characterized by TEM and DLS. Spectrum of Nb@IC-NPs towards NTR was measured by UV and fluorescence, while the particle’s selective response was studied using fluorescence. The uptake of Nb@IC-NPs in A549 cells was observed by flow cytometry and CLSM. In the meantime, its’ catalytic ability that decomposes H2O2 both extra-and intra-cellular was observed by fluorescence and CLSM. In vitro photodynamic toxicity of Nb@IC-NPs was examined by MTT, Live/Dead Cell Staining, Flow Cytometry and Apoptosis Assay. Tumor-bearing model was constructed to observe a semi-quantitative fluorescent distribution and the possibility of NIR-II fluorescence/photoacoustic (PA) imaging. Effect of Nb@IC-NPs on enhancing A549 tumor hypoxia and expression profile of HIF-1α was investigated in the presence of NIR. An A549 tumor metastasis model was also constructed to confirm the complex’ potential to destroy primary tumor, inhibit lung metastasis, and prolong mice’ survival. Lastly, impact of Nb@IC-NPs on mice’ main organs and blood indices was observed.Results Nb@IC-NPs was successfully fabricated with good homogeneity. The fluorescent absorbance of Nb@IC-NPs showed a linear relationship with the concentration of NTR, and a higher concentration of NTR corresponded to a stronger photoacoustic signal. In addition, Nb@IC-NPs showed a stable selectivity toward NTR. Our results also suggested a high efficient uptake of Nb@IC-NPs in A549 cells, which was more efficient than IC-NPs and IR1048-MZ alone. In vitro assays confirmed the effects of Nb@IC-NPs on catalytic O2 generation even in hypoxic cells. The cell viability was upregulated with the nanocomplex at the absence of the laser, whereas it was dramatically declined with laser treatment that excited at 980 nm. Nb@IC-NPs achieved tumor hypoxia NIR-II/PA imaging through assisting A549 gathering. When NIR was applied, Nb@IC-NPs can significantly relieve A549 cellular/tumor hypoxia by generating more reactive oxygen species (ROS), which in turn helps lower the expression level of HIF-1α. In summary, Nb@IC-NPs based PDT can efficiently decimate A549 primary tumor, inhibit metastatic lung cancer, and prolong the lifespan of the mice under tolerable dosage. At last, in vivo toxicity tests of the nanocomplex showed its biosafety to the main organs and normal blood indices values.Conclusion Nb@IC-NPs improves tumor hypoxia through catalytic reaction and lowers the expression level of HIF-1α. It achieves tumor PA imaging through intensified NIR-II fluorescence signal that caused by response of the complex to the lesion’s nitroreductase (NTR). Nb@IC-NPs based PDT can efficiently kill A549 primary tumor, inhibit a lung metastasis, as well as prolong mice’ survival cycle.
研究领域:
癌症研究
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生物医学工程
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药学
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分子生物学
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成像科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2021
·
IF 5.645
Yi Hong,Xiongli Liu,Huijuan Wang,Min Zhang,Minyi Tian
Alpinia coriandriodora is widely cultivated as a medicinal and edible Zingiberaceae plant in Guangxi, China. Since essential oils from Zingiberaceae plants can be used as a potential source of anticancer drugs, this study was designed to identify the chemical composition of A. coriandriodora rhizome essential oil (EO) and firstly elucidate its anticancer activities and related mechanisms. The GC-FID/MS results indicated that the most predominant component of EO was ( E )-2-decenal (56.3%). Based on the MTT results, EO exhibited comparable cytotoxicity to A549 cells and lower cytotoxicity to non-cancerous cells compared with the positive control (elemene injection). For related mechanism studies, EO inhibited the A549 cells proliferation, resulting from inducing cell cycle arrest at G1 phase via downregulation of cyclin E2-CDK2 and cyclin D3-CDK4/CDK6 complexes and upregulation of p21. Meanwhile, it induced the apoptosis through mitochondrial pathway with the successive enhancement in the Bax/Bcl-2 ratio, Δ ψ m decline, cyt c release, activation of caspase-9 and caspase-3, and PARP cleavage. Moreover, it inhibited the migration and invasion ability of A549 cells via downregulation of MMP-2 and N-cadherin, as well as upregulation of E-cadherin. Hence, EO has outstanding anticancer properties in vitro, and this fact encourages further studies using in vivo models.
研究领域:
药理学
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肿瘤学
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植物科学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2016
·
IF 4.219
Xinyu Hu,Yongmei Wang,Liangliang Zhang,Man Xu,Wei Dong,Jianfa Zhang
Salecan is a novel water-soluble extracellular β-glucan and possesses excellent physicochemical and biological properties. Here, redox/pH dual stimuli-responsive hydrogel based on Salecan grafted with itaconic acid (IA) and 2-hydroxyethyl methacrylate (HEMA) were prepared using disulfide-functionalized crosslinker N,N - bis (acryloyl)cystamine (BAC) for controlled drug delivery. The introduction of carboxylic groups endows the system with pH-sensitive character, swelling behavior of the hydrogel was conducted by changing the pH and Salecan content. It was demonstrated that DOX was efficiently loaded into the hydrogels and released in a controlled fashion via pH-control and swelling-shrinking mechanism. More importantly, DOX-loaded hydrogels showed dose dependent cytotoxicity toward A549 cell, and efficient cell killing was observed. Furthermore, a key point of this study was that the presence of disulfide linkage in system favored the degradation of hydrogels in the reductive environment. These results highlight the potential of Salecan- g -SS-poly(IA- co -HEMA) hydrogel as a novel system for the controlled release of anti-cancer drugs.
研究领域:
药学
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2022
·
IF 1.097
Tiandi Ding,HaiJiao Chen,Yan Li,Ying Li,Ying Zhi,Zhiqiang Qu,Qiang Sun,Qingqiang Yao,Bo Liu
Sphingosine kinase is a lipid kinase that catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate. Sphingosine-1-phosphate is a bioactive lipid that regulates biological processes. The overexpression of sphingosine kinases is related to a variety of pathophysiological conditions. For example, SphK1 has been shown to be highly expressed in various cancer cells including ovarian, cervical, colon, stomach, lung, and brain cancer. Inhibition of sphingosine kinases is a promising way to treat diseases such as cancer. Through computer-aided drug design, we have discovered a new SphK1 inhibitor named Amb30572637 (SAMS10). In this report, we describe the discovery process and biological characteristics. In biochemical experiments, SAMS10 shows a prominent inhibitory effect on SphK1, with an IC50 value of 9.8 μM. Subsequent MTT experiments show that SAMS10 has anticancer effects toward A549, SKVO3, A375, and LOVO cell lines and has essentially no cytotoxicity against the healthy cell L929. SAMS10 has significant inhibitory activity against the A549 and LOVO cell lines, with IC50 values of 14.64 and 14.48 μM, respectively. It belongs to a moderately active SphK1 inhibitor with lower anticancer activity than the control compound cisplatin, but the effect of SAMS10 toward SphK1 and its anticancer activity indicate that it is a promising lead compound for the development of effective SphK1 anticancer inhibitors.
研究领域:
药理学
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癌症研究
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药物发现
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生物化学
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分子生物学
✓ 已验证
DOI
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Guo Wei,Ma Xingyuan,Fu Yunhui,Liu Chang,Liu Qiuli,Hu Fabiao,Miao Hui,Zhang Tong,Liu Yuping,Han Myong Hun,You Fang,Yang Yi,Zheng Wenyun
Survivin as a member of the inhibitor of apoptosis proteins (IAPs) family is undetectable in normal cells, but highly expressed in cancer cells and cancer stem cells (CSCs) which makes it an attractive target in cancer therapy. Survivin dominant negative mutants have been reported as competitive inhibitors of endogenous survivin protein in cancer cells. However, there is a lack of systematic comparative studies on which mutants have stronger effect on promoting apoptosis in cancer cells, which will hinder the development of novel anti-cancer drugs. Here, based on the previous study of survivin and its analysis of the relationship between structure and function, we designed and constructed a series of different amino acid mutants from survivin (TmSm34, TmSm48, TmSm84, TmSm34/48, TmSm34/84, and TmSm34/48/84) fused cell-permeable peptide TATm at the N-terminus, and a dominant negative mutant TmSm34/84 with stronger pro-apoptotic activity was selected and evaluated systematically in vitro. The double-site mutant of survivin (TmSm34/84) showed more robust pro-apoptotic activity against A549 cells than others, and could reverse the resistance of A549 CSCs to adriamycin (ADM) (reversal index up to 7.01) by decreasing the expression levels of survivin, P-gp, and Bcl-2 while increasing cleaved caspase-3 in CSCs. This study indicated the selected survivin dominant negative mutant TmSm34/84 is promising to be an excellent candidate for recombinant anti-cancer protein by promoting apoptosis of cancer cells and their stem cells and sensitizing chemotherapeutic drugs.
研究领域:
肿瘤学
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分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 8
·2255
·
IF 4.412
Nan Wei,Jun Zhao,Guimei Wu,Wenjuan Cao,Pei Luo,Zhifeng Zhang,Gang Chen,Lu Wen
As a consequence of recent progression in biomedicine and nanotechnology, nanoparticle-based systems have evolved as a new method with extensive applications in responsive therapy, multimodal imaging, drug delivery and natural product separation. Meanwhile, the magnetic nanoparticulate system has aroused great interest for separation and purification because of its excellent magnetic properties. Phospholipase A2(PLA2) is a highly expressed regulator to promote the growth of various cancers and is an ideal target to treat cancers. In this study, a novel strategy based on ligand–receptor interactions to discover novel PLA2inhibitors was established, in which PLA2-functionalized Fe3O4@PLGA-PEG-NH2magnetic nanoparticles were used as a supporting material combined with high-performance liquid chromatography–mass spectrometry, aiming to accelerate the discovery of novel PLA2inhibitors from natural sources such as mangrove endophytic fungi. Under the optimized ligand fishing conditions, six target compounds were ultimately fished and identified to be cyclic peptides (1–3) and sterols (4–6), which compounds1,2and4–6have well-documented cytotoxicities. Compound3exerted better inhibitory effect on A549 cells by experiment. In conclusion, PLA2-functionalized Fe3O4@PLGA-PEG-NH2magnetic nanoparticles-based ligand fishing provided a feasible, selective and effective platform for the efficient screening and identification of antitumor components from natural products.Keywords:magnetic nanoparticles;ligand fishing;phospholipase A2;endophytic fungus
研究领域:
生物医学工程
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纳米技术
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药理学
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真菌学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2021
·Vol. 32
·期 37
·375712
·
IF 3.874
Bin Nie,Hong Wang,Chaohui Rao,Yanwei Zhang,Huifang Wang,Xiaojie Lian,Xianghua Gao,Baolong Niu,Wenfeng Li
Phosphate-stabilized amorphous calcium carbonate (ACCP) has excellent biocompatibility, bioactivity, and biodegradability, and can be easily synthesized and stored. However, unmodified ACCP, as a controlled drug release carrier, decomposes rapidly in an acidic environment and highly depends on the system's pH value, which can not meet the need for long-term release of active substances, thus limiting its application scope. To realize the specific pH responsiveness of ACCP nanoparticles, we designed and synthesized monodisperse sodium alginate/ACCP (Alginate/ACCP) composite nanoparticles in this paper. After ultrasonic treatment, nanoparticles with an average particle size less than 200 nm could form stable water dispersion that could be dispersed for up to 10 d. Based on the specific pH sensitivity of sodium alginate, the drug-controlled release performance of composite nanoparticles and the therapeutic effect of drug-loaded nanoparticles on A549 cancer cells were studied. The results indicated that under the same pH condition, the curcumin (Cur) release rate of composite nanoparticles gradually decreased with sodium alginate addition. When the dosage of sodium alginate was 1.0 mg ml−1, the cumulative drug release rate of nanoparticles in 40 h was only about 35%. Besides, the drug-loaded nanoparticles showed the excellent killing ability of cancer cells, and the survival rate of cancer cells decreased in a concentration-dependent manner. Therefore, through reasonable optimization design, we can synthesize composite nanoparticles with excellent sustained-release properties to provide a new strategy for cancer cells' long-term treatment.
研究领域:
纳米技术
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药学
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2017
·Vol. 52
·期 5
·1176-1184
·
IF 1.64
Jing Li,Wenting Shang,Xu Si,Dandan Bu,Padraig Strappe,Zhongkai Zhou,Chris Blanchard
Summary Corn bran polysaccharides were extracted using an ultrasonic-assisted method with a yield of 33.50% and then carboxymethylated. The occurrence of modification was confirmed using Fourier transform infrared spectral analysis. The surface of polysaccharide particles became loosened following the carboxymethylation. The effect of sodium hydroxide concentration, reaction temperature, and the reaction time on the degree of substitution was investigated, and the relationship among the substitution degree, total phenolic content and antioxidant activity were studied. With sodium hydroxide concentration of 6.0 mol L −1 , keeping the reaction temperature of 60 °C and reaction time of 5.0 h, the modified polysaccharides possessed the highest degree of substitution and antioxidant activity. Cell culture model indicated that the carboxymethylated polysaccharide significantly inhibited the proliferation of A549 and HepG-2 cells, and these antitumour characteristics may be associated with the elevated expression of CASP3 , CASP8 , CASP9 , and p53 , as well as the significantly decreased expression of Bcl-2 and iNOS genes. The excellent antioxidant capacity and strong antitumour activity of these polysaccharides might provide a potential application as a naturally functional ingredient.
研究领域:
食品科学
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生物化学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Yixin Dong,Kun Yang,Zicheng Xu,Xun Li,Fei Wang,Yu Zhang
The application of drug delivery systems based on ferritin nanocarrier has been developed as a potential strategy in cancer therapy. The limited permeability of ferritin remains a challenge for drug penetration into the deeper tumor tissues. CendR peptides have been reported to bear tumor-specific penetration by recognizing neuropilin (NRP-1) receptor that overexpressed on a wide range of cancer cells. Herein, we modified CendR peptide L(RGERPPR), its retro-inverso peptide D(RPPREGR), and inverso peptide D(RGERPPR) on the outer surface of human H chain ferritin by sulfhydryl-maleimide coupling reaction. Approximately 45 paclitaxel (PTX) molecules could be loaded into each ferritin inner cavity by a thermal-triggered method at a specific ionic strength. The penetration ability of three peptide-modified ferritin constructs showed that D(RGERPPR)-modified HFtn was able to be engulfed by A549 and MCF-7 tumor cells and spheroids at the highest level. Due to the dual-targeting effect of ferritin and modified peptides, the PTX-loaded nanocomposites could effectively enter the cells with high expression of TfR1 and NRP-1 receptors and enhanced the cytotoxicity against tumor cells. Remarkably, H-D(RGE)-PTX displayed a superior tumor growth suppression efficacy in A549 tumor-bearing nude mice. The inverso CendR peptide-modified HFtn nanocarrier was first generated and could provide an effective dual-targeting platform for treatment of cancers.
研究领域:
药学
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癌症研究
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纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 17
·3990
·
IF 4.2
Shuang Tian,Yinxu Zhao,Siqi Deng,Liman Hou,Juan Song,Ming Wang,Ming Bu
In the following study, a series of new lupeol-3-carbamate derivatives were synthesized, and the structures of all the newly derived compounds were characterized. The new compounds were screened to determine their anti-proliferative activity against human lung cancer cell line A549, human liver cancer cell line HepG2, and human breast cancer cell line MCF-7. Most of the compounds were found to show better anti-proliferative activity in vitro than lupeol. Among them, obvious anti-proliferation activity (IC50= 5.39~9.43 μM) was exhibited by compound3iagainst all three tumor cell lines. In addition, a salt reaction was performed on compound3k(IC50= 13.98 μM) and it was observed that the anti-proliferative activity and water solubility of compound3k·CH3I(IC50= 3.13 μM), were significantly enhanced subsequent to the salt formation process. The preliminary mechanistic studies demonstrated that apoptosis in HepG2 cells was induced by compound3k·CH3Ithrough the inhibition of the PI3K/AKT/mTOR pathway. In conclusion, a series of new lupeol-3-carbamate derivatives were synthesized via the structural modification of the C-3 site of lupeol, thus laying a theoretical foundation for the design of this new anticancer drug.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 43
·9031-9040
·
IF 6.331
Jilin Zheng,Peng Zhao,Shiying Zhou,Sha Chen,Yi Liang,Fengchun Tian,Jun Zhou,Danqun Huo,Changjun Hou
Integrating metal–organic frameworks (MOFs) of different components or structures together and exploiting them as electrochemical sensors for electrochemical sensing has aroused great interest. Furthermore, the incorporation of noble metals with MOFs is conducive to the improvement of catalytic performance. In this work, Pd@UiO-66-on-ZIF-L nanomaterials were successfully synthesised onto a self-supported flexible carbon cloth (Pd@UiO-66-on-ZIF-L/CC) through a novel strategy called MOF-on-MOF. Then, Au nanoparticles were electrodeposited onto Pd@UiO-66-on-ZIF-L/CC to obtain Au–Pd@UiO-66-on-ZIF-L/CC, which can serve as an excellent electrocatalyst for the reduction of hydrogen peroxide (H2O2). The obtained flower-like Pd@UiO-66-on-ZIF-L/CC hybrid MOF changes the structure of the monomeric MOF alone and adds more attachment sites. The synergy of the bimetals greatly improved the catalytic performance of the as-developed sensor. Electrochemical experiment results show that the proposed sensor based on Au–Pd@UiO-66-on-ZIF-L/CC has an extended linear range from 1 μM to 19.6 mM with a sensitivity of 390 μA mM−1 cm−2, and a low limit of detection (LOD) of 21.2 nM (S/N = 3). Moreover, it has good anti-interference, reproducibility, repeatability and excellent stability. Furthermore, the real-time in situ detection of H2O2 secreted from human adenocarcinomic alveolar basal epithelial cells (A549 cells) was achieved by culturing cells on Au–Pd@UiO-66-on-ZIF-L/CC, which indicates the potential of the sensor for applications in cancer pathology. Both the synthesis strategy and the sensor design provide new methods and ideas for the production of ultrasensitive H2O2 electrochemical sensors.
研究领域:
材料科学
·
电化学
·
生物传感器
·
癌症病理学
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Zhen-Dong Zhang,Ya-Jun Yang,Xi-Wang Liu,Zhe Qin,Shi-Hong Li,Jian-Yong Li
Paraquat (PQ) is an effective and commercially important herbicide that is widely used worldwide. However, PQ is highly toxic and can cause various complications and acute organ damage. Aspirin eugenol ester (AEE) is a potential new compound with anti-inflammatory and antioxidant stress pharmacological activity. The present study was to reveal the therapeutic effects and the protective effect of AEE against PQ-induced acute lung injury (ALI) with the help of PQ-induced oxidative damage in A549 cells and PQ-induced lung injury in rats. AEE might have no significant therapeutic effect on PQ-induced lung injury in rats. However, AEE had a significant protective effect on PQ-induced lung injury in rats. AEE pretreatment significantly reduced the stimulatory effect of PQ on malondialdehyde (MDA), the inhibitory effect of PQ on catalase (CAT) activity, superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, the ratio of GSH/GSSH, the activity of caspase-3 and the overexpression of p38 mitogen-activated protein kinase (MAPK) phosphorylation in vivo . In vitro , A549 cells were treated with 250 μM PQ for 24 h. Incubation of A549 cells with PQ led to apoptosis, and increased the level of superoxide anions, reactive oxygen species (ROS), malondialdehyde and the activity of caspase-3 and up-regulation of phosphorylated p38-MAPK, reduced mitochondrial membrane potential (ΔΨm) and the activity of SOD. However, after 24 h on AEE pretreatment of A549 cells, the above-mentioned adverse reactions caused by PQ were significantly alleviated. In addition, AEE pretreatment reduced p38-MAPK phosphorylation in PQ-treated A549 cells. SB203580, the specific p38-MAPK inhibitor, and p38-MAPK shRNA attenuated the activation of the p38-MAPK signaling pathway. N-acetylcysteine (NAC) reduced the level of phosphorylated p38-MAPK and the production of intracellular ROS and inhibited apoptosis. The results showed that AEE may inhibit PQ-induced cell damage through ROS/p38-MAPK-mediated mitochondrial apoptosis pathway.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）