Pharmaceutics
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2019
·Vol. 11
·期 3
·123
·
IF 4.773
Jun Ding,Guilin Chen,Guofang Chen,Mingquan Guo
Epirubicin-capped silver nanoparticles (NPs) were synthesized through a one-pot method by using epirubicin as both the functional drug and the reducing agent of Ag+to Ag0. The preparation process was accomplished in 1 h. In addition, the obtained epirubicin-capped silver nanoparticle was characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and infrared spectroscopy. The results showed that a layer of polymer epirubicin had formed around the silver nanoparticle, which was 30-40 nm in diameter. We further investigated the antitumor activity of the prepared epirubicin-capped silver nanoparticle, and the half maximal inhibitory concentration (IC50) against Hep G2 cells was 1.92 μg/mL, indicating a good antitumor property of the nanoparticle at low dosage.Keywords:epirubicin;one-pot synthesis;silver nanoparticle;antitumor
研究领域:
药学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Chemistry Central Journal
·
2016
·Vol. 10
·期 1
·1-11
·
IF 2.552
Mo Wei-bin,Su Chun-hua,Huang Jia-yan,Liu Jun,Chen Zhen-feng,Cheng Ke-guang
Background Oleanolic acid, which can be isolated from many foods and medicinal plants, has been reported to possess diverse biological activities. It has been found that the acylation of the hydroxyl groups of the A-ring in the triterpene skeleton of oleanolic acid could be favorable for biological activities. The pyrimidinyl group has been constructed in many new compounds in various anti-tumor studies.Results Five acyl oleanolic acid-uracil conjugates were synthesized. Most of the IC50 values of these conjugates were lower than 10.0 μM, and some of them were even under 0.1 μM. Cytotoxicity selectivity detection revealed that conjugate 4c exhibited low cytotoxicity towards the normal human liver cell line HL-7702. Further studies revealed that 4c clearly possessed apoptosis inducing effects, could arrest the Hep-G2 cell line in the G1 phase, induce late-stage apoptosis, and activate effector caspase-3/9 to trigger apoptosis.Conclusion sConjugates of five different acyl OA derivatives with uracil were synthesized and identified as possessing high selectivity toward tumor cell lines. These conjugates could induce apoptosis in Hep-G2 cells by triggering caspase-3/9 activity.Five acyl oleanolic aicd-uracil conjugates were synthesized. These conjugates exhibited selective cytotoxicity toward tumor cells achieved via inducing apoptosis by activation of caspase-3/9.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2022
·
IF 11.357
Di Zhang,Tom Bond,Yang Pan,Mingli Li,Jiayi Luo,Rong Xiao,Wenhai Chu
Identifying disinfection byproducts (DBPs) with high health risk is an unresolved challenge. In this study, six members of a new class of aromatic nitrogenous DBPs─2-chloroaniline, 2-bromoaniline, 2,4-dichloroaniline, 2-chloro-4-bromoaniline, 4-chloro-3-nitroaniline, and 2-chloro-4-nitroaniline─are reported as DBPs in drinking water for the first time. Haloanilines completely degraded within 1 h in the presence of chlorine (1 mg/L), while about 20% remained in the presence of chloramine (1 mg/L) after 120 h. Haloanilines showed high stability in the absence of disinfectants, with <30% degradation at pH 5–9 over 120 h. Eight haloanilines were determined in chloraminated finished water and tap water at total concentrations of up to 443 ng/L. The most abundant was 2-bromoaniline, with a median concentration of 104 ng/L. The cytotoxicity of eight haloanilines and regulated trichloromethane and dichloroacetic acid (DCAA) was evaluated using Hep G2 cell assay. The EC50 values of eight haloanilines were 1–2 orders of magnitude lower than those of the regulated DBPs. The lowest toxic concentration of 2-chloro-4-nitroaniline was 1 μM, 500 times lower than that of DCAA. The formation and control of haloanilines in drinking water warrant further investigation.
研究领域:
环境科学
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水处理
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毒理学
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公共卫生
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Huiqi Li,Qizhuan Lin,Huanpeng Liu,Zheyan Chen,Xueliang Zhang,Liyuan Jin,Renyi Peng,Huanzhi Jin
Polystyrene nanoplastics (PS-NPs) and copper ions (Cu²⁺) are common environmental pollutants, yet their combined toxicological effects remain poorly understood. This study demonstrates that PS-NPs act as carriers of Cu²⁺, facilitating intracellular accumulation and inducing cuproptosis, a recently identified form of regulated cell death. Using zebrafish larvae and Hep G2 cells, we showed that co-exposure to PS-NPs and Cu²⁺ disrupted copper homeostasis, promoted DLAT oligomerization, impaired mitochondrial structure and function, and activated the cuproptosis pathway. Molecular docking revealed stable binding of PS-NPs and Cu²⁺ to the key regulator FDX1, further aggravating cuproptosis. FDX1 overexpression experiments confirmed its pivotal role, as enhanced expression significantly increased DLAT aggregation and cell death. This study is the first to reveal the molecular mechanism by which PS-NPs mediate FDX1-dependent cuproptosis via a “Trojan horse” effect. These findings provide novel insights into the mechanisms of nanoplastics–heavy metal co-exposure and offer a potential molecular target for mitigating environmental toxicity.
研究领域:
环境毒理学
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细胞生物学
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纳米毒理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2019
·
IF 0
Hongyan Cui,Jing Xia,Liuwei Zhang,Ming Qian,Hao Wang,Jingyun Wang,Qixian Chen
The surface properties of drug/gene delivery systems are critical important to their ultimate therapeutic performance. In the present studies, cytoplasmic membranes deriving from cancerous cells (Hep-G2) were attempted as the external integument onto the polycationic theranostic DNA delivery systems with the aim of diminishing unfavorable biointerfacial reactions of nanomedicine. Herein, a multiple of polycationic oligoethylenimine (OEI) segments were installed onto the surface of luminescent carbon quantum dots (CQD, facile bioimaging utilities) for complexation with plasmid DNA (pDNA) into DNA delivery constructs, followed by surface integument by cytoplasmic membranes. The subsequent investigations verified this strategic integument capable of shielding the unfavorable surface positive net charge of the polycationic DNA delivery constructs and thereby markedly diminishing the potential nonspecific reactions in biological milieu. Leadingly, improved biocompatibilities as well as additional protection of inner vulnerable DNA cargos from enzymatic degradation, have been accomplished. More importantly, preferential affinities to the homologous cells were identified as a result of this membrane integument based on facile fluorescence quantification for the intracellular CQD. Significant higher cellular uptake efficiency for the polycationic constructs based on Hep-G2 membrane integument was confirmed in the homologous Hep-G2 cells in contrast to the heterologous MCF-7 and HeLa cells (approximately 4-fold). Note that this homologous privilege was observed for the delivery constructs not only from cancerous HeLa and MCF-7 membrane integuments but also normal cells (COS-7), heralding the intriguing potentials of this membrane-integument strategy in pursuit of targeting functions. Eventually, gene expression activities were also determined to prevail in the homologous cells. Therefore, our proposed surface integument strategy by homologous cell membrane could imply an alternative facile and versatile avenue in construction of active-targeted nanomedicine.
研究领域:
分子生物学
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纳米医学
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基因工程
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2021
·
IF 9.028
Yun Wu,Wenzhe Wei,Jiayi Luo,Yang Pan,Mengting Yang,Ming Hua,Wenhai Chu,Chendong Shuang,Aimin Li
In recent years, dozens of halogenated disinfection byproducts (DBPs) with cyclic structures were identified and detected in drinking water globally. Previous in vivo toxicity studies have shown that a few new cyclic DBPs possessed higher developmental toxicity and growth inhibition rate than common aliphatic DBPs; however, in vitro toxicity studies have proved that the latter exhibited higher cytotoxicity and genotoxicity than the former. Thus, to provide a more comprehensive toxicity comparison of DBPs from different endpoints, 11 groups of cyclic DBPs and nine groups of aliphatic DBPs were evaluated for their comparative in vitro and in vivo toxicity using human hepatoma cells (Hep G2) and zebrafish embryos. Notably, results showed that the in vitro Hep G2 cytotoxicity index of the aliphatic DBPs was nearly eight times higher than that of the cyclic DBPs, whereas the in vivo zebrafish embryo developmental/acute toxicity indexes of the cyclic DBPs were roughly 48–50 times higher than those of the aliphatic DBPs, indicating that the toxicity rank order differed when different endpoints were applied. For a broader comparison, a Pearson correlation analysis of DBP toxicity data from nine different endpoints was conducted. It was found that the observed Hep G2 cytotoxicity and zebrafish embryo developmental/acute toxicity in this study were highly correlated with the previously reported in vitro CHO cytotoxicity and in vivo toxicity in aquatic organisms (P < 0.01), respectively. However, the observed in vitro toxicity had no correlation with the in vivo toxicity (P > 0.05), suggesting that the toxicity rank orders obtained from in vitro and in vivo bioassays had large discrepancies. According to the observed toxicity data in this study and the candidate descriptors, two quantitative structure–activity relationship (QSAR) models were established, which help to further interpret the toxicity mechanisms of DBPs from different endpoints.
研究领域:
环境科学
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毒理学
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化学工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2015
·
IF 8.557
Yang Wang,Ruibo Zhao,Shibing Wang,Zhaoming Liu,Ruikang Tang
Multidrug resistance is one of major obstacles to the effective cancer chemotherapy. To address this issue, we developed the effective circumvention of multidrug resistance in cancer cells by a yolk-shell Fe 3 O 4 @MgSiO 3 nanoplatform with the polymerpoly(ethylene glycol) and folic acid modifications can achieve active targeted delivery of anti-cancer drug by using combined magnetic and ligand targeting . The direct intracellular drug delivery of doxorubicin by nanocarrier was much more effectively than free DOX for multidrug resistant Hep-G2/MDR cancer cells. Besides the excellent biocompatibility, high drug loading efficiency, dual-targeting delivery, and controlled releasing behavior, in vivo experiments demonstrate that this nanocarrier can specifically deliver and concentrate doxorubicin hydrochloride in tumor sites to overcome drug resistance. It follows an alternative strategy for effective chemotherapy against drug resistant cancers by using rationally designed nanomaterial .
研究领域:
癌症研究
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纳米技术
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药学
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材料科学
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产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2021
·Vol. 11
·期 5
·1440-1451
·
IF 2.693
Tianyu Wu,Sichun Zhou,Mei Qin,Jing Tang,Xinjian Yan,Lingli Huang,Meiyuan Huang,Jun Deng,Di Xiao,Xin Hu,Jingtao Wu,Xiaoping Yang,Gaofeng Li
Inhibitors of ataxia – telangiectasia mutated (ATM), such as KU-55933 (Ku), represent a promising class of novel anticancer drugs. In addition, the biguanide derivative phenformin exhibits antitumor activity superior to that of the AMPK activator metformin. Herein, we assessed the potential combinatorial therapeutic efficacy of phenformin and Ku when used to inhibit the growth of liver cancer cells, and we assessed the mechanisms underlying such efficacy. The Hep-G2 and SMMC-7721 liver cancer cell lines were treated with phenformin and Ku either alone or in combination, after which the impact of these drugs on cellular proliferation was assessed via 3-(4,5-dimethylthiazol) 2, 5-diphenyltetrazolium and colony formation assays, whereas Transwell assays were used to gauge cell migratory activity. The potential synergy between these two drugs was assessed using the CompuSyn software, while flow cytometry was employed to evaluate cellular apoptosis. In addition, western blotting was utilized to measure p-ATM, p-AMPK, p-mTOR, and p-p70s6k expression, while mitochondrial functionality was monitored via morphological analyses, JC-1 staining, and measurements of ATP levels. Phenformin and Ku synergistically impacted the proliferation, migration, and apoptotic death of liver cancer cells. Together, these compounds were able to enhance AMPK phosphorylation while inhibiting the phosphorylation of mTOR and p70s6k. These data also revealed that phenformin and Ku induced mitochondrial dysfunction as evidenced by impaired ATP synthesis, mitochondrial membrane potential, and abnormal mitochondrial morphology. These findings suggest that combination treatment with phenformin and Ku may be an effective approach to treating liver cancer via damaging mitochondria within these tumor cells.
研究领域:
肿瘤学
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药理学
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细胞生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Xingzheng Liu,Junsheng Jin,Yueliang Chen,Boting Lu,Qian Sun,Jiexin Wang,Jian-feng Chen,Yuan Le
Poly ( n -butyl cyanoacrylate) (PBCA) nanoparticles are widely used as biocompatible and bio-erosive materials in a range of biomedical applications, especially for drug delivery systems. This paper reports a novel synthesis method of PBCA nanoparticles with high productivities and purities in a rotating packed bed. The particle size and molecular weight of PBCA nanoparticles were controlled by adjusting the high-gravity factor, surfactant concentration, pH, temperature and monomer concentration. The high-gravity factor shows an obvious influence on the particle sizes, while it has few effects on molecular weight. The surfactant concentration and pH also affect molecular weight and particle sizes. Moreover, compared with conventional stirred tank, the reaction time of RPB procedure was dramatically reduced from 12 h to 2 h, and the purity of products increased from about 93% to 96%. Furthermore, when the molecular weight of PBCA increased, the in vitro cytotoxicity to Hep G2 cells firstly increased and then decreased, and the cellular uptake was improved. In summary, PBCA with controllable molecular weight and particle sizes can be synthesized using a facile high-gravity method.
研究领域:
材料科学
·
生物医学工程
·
纳米技术
·
药学
✓ 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）