Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Zideng Dai,Xinyu Xu,Zhaoming Guo,Kun Zheng,Xue-Zhi Song,Xiuyu Qi,Zhenquan Tan
Ultra-thin two-dimensional nanosheets have attracted increasing attention due to their great application prospects in nanomaterial science and biomedicine. Herein, we report the preparation of exfoliated raw and oxidized 4-layer Ti 7 O 13 (O-Ti 7 O 13 ) and their ability to produce reactive oxygen species (ROS). The results show that O-Ti 7 O 13 nanosheets can effectively produce ROS induced by X-ray irradiation. The 4-layer nanosheets can quickly load doxorubicin (DOX) within 5 min with a high loading rate to obtain a novel nanodrug system through their electrostatic adsorption capacity, and they exhibit a sustained release behavior. In this way, chemotherapy, radiation therapy and photodynamic therapy effectively combine for cancer synergistic treatment. We evaluated the cytotoxicity, cellular uptake and intracellular location of the O-Ti 7 O 13 nanosheet-based drug delivery system in A549 lung cancer cells. Our results show that the O-Ti 7 O 13 /DOX complex is more cytotoxic to A549 cells than free DOX since a low concentration of loaded DOX (10 μg/mL) with a low dose of X-rays can cause the complete apoptosis of tumor cells. This work reveals that the therapeutic effect of DOX-loaded O-Ti 7 O 13 nanosheets is strongly dependent on their loading mode, and the effects of chemotherapy and photodynamic therapy are enhanced under X-ray irradiation, which allows O-Ti 7 O 13 nanosheet use as a photo-activated drug carrier. This work provides a new strategy for preparing 2D metal oxide nanosheets toward biomedical applications.
研究领域:
纳米材料科学
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生物医学
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癌症治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2021
·Vol. 168
·期 12
·127501
·
IF 4.316
Shiying Zhou,Human Sun,Xianfeng Wang,Peng Lu,Danqun Huo,Jiawei Li,Xiaogang Luo,Changjun Hou
Real-time detection of extracellular hydrogen peroxide is important for dynamic monitoring of diseases and cytopathological research. Here, a novel composite of Fe-hemin-metal organic frameworks/three-dimensional graphene (Fe-hemin MOFs/3DG) was prepared by embedding hemin into amino-contained Fe-MOFs, then decorated with 3DG. The obtained Fe-hemin MOFs/3DG possessed efficient peroxidase-like bioactivity and could serve as an effective catalyst for construction of H2O2 electrochemical sensor. The electrochemical results show that the proposed sensor based on Fe-hemin MOFs/3DG has excellent catalytic activity for H2O2. With a linear range was 10−12080 μM and LOD was 0.34 μM, this sensor showed favorable selectivity, repeatability and stability, which could be used to detect H2O2 in real serum samples. Most importantly, this sensor realized the real-time determination of H2O2 released by A549 cells and possessed good biocompatibility. The outstanding electrochemical performance mainly benefited from the unique porous structure of MOFs, which could effectively protect the active center of hemin, and the introduction of 3DG greatly improved the conductivity of Fe-hemin MOFs. Therefore, the Fe-hemin MOFs/3DG could be a promising probe for real-time dynamic monitoring of H2O2.
研究领域:
材料科学
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分析化学
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生物传感器
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生物医学工程
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DOI
高影响因子
BMC Complementary Medicine and Therapies
·
2020
·Vol. 20
·期 1
·1-9
·
IF 0
Li Jiashun,Jie Xiang,Liang Xiaoli,Chen Ziyu,Xie Peifang,Pan Xiping,Zhou Beixian,Li Jing
Background Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the anti-inflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations. Methods The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virus-triggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. Results Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E 2 (PGE 2 ) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings. Conclusion Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.
研究领域:
药理学
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免疫学
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病毒学
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细胞生物学
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产品关联
DOI
PubMed
Materials
·
2019
·Vol. 12
·期 5
·766
·
IF 2.972
Yan Li,Fangxiang Song,Liang Cheng,Jin Qian,Qianlin Chen
Large-pore coralline mesoporous silica microparticles (CMS) were synthesized using the triblock polymer PEG-b-PEO-b-PEG and a hydrothermal method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the coralline morphology of the fabricated materials. The Brunauer–Emmett–Teller (BET) method and the Barrett–Joyner–Halenda (BJH) model confirmed the existence of large pores (20 nm) and of a tremendous specific surface area (663.865 m2·g−1) and pore volume (0.365 cm3·g−1). A novel pH-sensitive multiamine-chain carboxyl-functionalized coralline mesoporous silica material (CMS–(NH)3–COOH) was obtained via a facile “grafting-to” approach. X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) validated the effective interfacial functionalization of CMS with carboxyl and multiamine chains. The encapsulation and release behavior of the dual drug (gefitinib (GB) and doxorubicin (DOX)) was also investigated. It was found that CMS–(NH)3–COOH allows rapid encapsulation with a high loading capacity of 47.36% for GB and 26.74% for DOX. Furthermore, the release profiles reveal that CMS–(NH)3–COOH can preferably control the release of DOX and GB. The accumulative release rates of DOX and GB were 32.03% and 13.66%, respectively, at a low pH (pH 5.0), while they reduced to 8.45% and 4.83% at pH 7.4. Moreover, all of the modified silica nanoparticles exhibited a high biocompatibility with a low cytotoxicity. In particular, the cytotoxicity of both of these two drugs was remarkably reduced after being encapsulated. CMS–(NH)3–COOH@GB@DOX showed tremendously synergistic effects of the dual drug in the antiproliferation and apoptosis of A549 human cancer cells in vitro.Keywords:mesoporous silica;multiamine chains;carboxylation;interfacial functionalization;great synergistic effects
研究领域:
材料科学
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药学
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2015
·Vol. 182
·期 9
·1827-1834
·
IF 3.741
Li Yang,Chen Ruchun,Li Yiyang,Sharafudeen Kaniyarakkal,Liu Shijian,Wu Dakun,Wu Yiling,Qin Xixi,Qiu Jianrong
Folic acid-conjugated luminescent nanomaterials have long been widely used in targeted bioimaging, often simultaneously acting as vehicles for drug delivery. They often require, however, intense light sources for photoexcitation, and this often results in photobleaching, strong luminescence background, and strong light scattering. This article describes the preparation of nanoparticles (NPs) of the type Zn 1.1 Ga 1.8 Sn 0.1 O 4 doped with Cr(III) ions and surface-modified with folic acid. The functionalization of the NPs was monitored via measurement of zeta potentials, FTIR spectra and thermogravimetry. Cell viability and biocompatibility were tested using the MTT kit. The NPs have a size of 220 nm and were characterized by dynamic X-ray diffraction, light scattering, field emission scanning electron microscopy and high-resolution transmission electron microscopy. After annealing the NPs for 10 min at 300 °C and irradiating them with 254 nm light for 10 min, they display deep red emission that persists for up to 10 h. The NPs are easily dispersed, small-sized, and crystalline. In our perception, the new material with its long decay time offers quite novel features in terms of targeted optical imaging in providing high resolution, weak disturbance by background luminescence, and the absence of light scattering. They were successfully applied to image MCF-7 and A549 cells.
Folic acid-conjugated nanoparticles of the type Zn 1.1 Ga 1.8 Sn 0.1 O 4 :Cr 3+ are presented that are easily dispersible, small-sized (100 nm), and well crystallized. They display a phosphorescence in the NIR that persists for >10 h after excitation and were used to image MCF-7 and A549 cells.
研究领域:
材料科学
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纳米技术
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生物医学工程
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癌症研究
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光学成像
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 23
·4455-4469
·
IF 4.543
Mengyun Zhou,Xin Du,Weike Li,Xiaoyu Li,Hongwei Huang,Qingliang Liao,Bingyang Shi,Xueji Zhang,Meiqin Zhang
Biodegradability is very critical for biomaterials to be nanocarriers. Ideal nanocarriers should be stable enough to execute their functions, but then can be efficiently got rid of, by either biodegradation or excretion. In this work, we report the design and one-pot fabrication of a series of uniform organic–inorganic hybrid nanocapsules with a disulfide-bridged silsesquioxane framework and a particle size smaller than 100 nm for redox-triggered biodegradation. The optimal synthesis conditions were explored for balancing the nanostructure, sulfur (S) content and aggregation degree. Fluorescent molecules were also integrated into the disulfide-bridged silsesquioxane framework by a co-condensation strategy for fluorescence tracking. Dithiothreitol (DTT) as a strong model reducing agent triggered the breakdown of hybrid nanocapsules without and with PEG modification from intact nanospheres to small fragments, while intracellular glutathione (GSH) had a slightly lower capacity of biodegrading these nanocapsules. The constructed delivery system obviously inhibited the growth of A549 cancer cells due to efficient cellular uptake by an endocytosis pathway and the subsequent pH and GSH-triggered drug release. The possibility of regulating the framework and surface functionalization of hybrid nanocapsules opens new opportunities for the development of silica-based degradable hybrid nanocarriers for promising drug delivery.
研究领域:
纳米技术
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材料科学
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药剂学
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生物材料
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Bo Zhang,Ting Jiang,Li Ling,Zhonglian Cao,Jingjing Zhao,Yanyan Tuo,Xiaojian She,Shun Shen,Xinguo Jiang,Yu Hu,Zhiqing Pang
Tumor stromal cells have been increasingly recognized to interact with tumor parenchyma cells and promote tumor growth. Therefore, we speculated that therapeutics delivery to both parenchyma cells and stromal cells simultaneously might treat a tumor more effectively. Tissue factor (TF) was shown to be extensively located in a tumor and was abundantly sited in both tumor parenchyma cells and stromal cells including neo-vascular cells, tumor-associated fibroblasts, and tumor-associated macrophages, indicating it might function as a favorable target for drug delivery to multiple cell types simultaneously. EGFP-EGF1 is a fusion protein derived from factor VII, the natural ligand of TF. It retains the specific TF binding capability but does not cause coagulation. In the present study, a nanoparticle modified with EGFP-EGF1 (ENP) was constructed as a multitargeting drug delivery system. The protein binding experiment showed EGFP-EGF1 could bind well to A549 tumor cells and other stromal cells including neo-vascular cells, tumor-associated fibroblasts, and tumor-associated macrophages. Compared with unmodified nanoparticles (NP), ENP uptake by A549 cells and those stromal cells was significantly enhanced but inhibited by excessive free EGFP-EGF1. In addition, ENP induced more A549 tumor cell apoptosis than Taxol and NP when paclitaxel (PTX) was loaded. In vivo, ENP accumulated more specially in TF-overexpressed A549 tumors by in vivo imaging, mainly regions unoccupied by factor VII and targeted tumor parenchyma cells as well as different types of stromal cells by immunofluorescence staining. Treatment with PTX-loaded ENP (ENP-PTX) significantly reduced the A549 tumor growth in nude mice while NP-PTX- and Taxol-treated mice had lower response to the therapy. Furthermore, H&E and TUNEL staining revealed that ENP-PTX induced more severe tumor necrosis and more extensive cell apoptosis. Altogether, the present study demonstrated that ENP could target multiple key cell types in tumors through TF, which could be utilized to improve the therapeutic effect of anticancer drugs.
研究领域:
癌症生物学
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药学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2023
·
IF 3.3
Peng-Cheng Zhong,Zhi-Wen Liu,Qi-Chang Xing,Jia Chen,Rui-Pei Yang
Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-β and MST1 were applied to validate the roles of TGF-β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-β in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Jiahui Zou,Xuyang Xing,Chao Teng,Qingling Zhao,Wei He,Xuri Wu,Yuanzheng Xia
Multidrug resistance (MDR), the major mechanism by which various cancers develop specific resistance to therapeutic agents, has set up enormous obstacles to many forms of tumor chemotherapy. Traditional cocktail therapy administration, based on the combination of multiple drugs for anti-MDR chemotherapy, often suffers from inconsistent in vivo pharmacokinetic behaviors that cannot act synchronously on the lesions, leading to limited pharmacodynamic outcomes. Despite the emergence of nanomedicines, which has improved chemotherapeutic drugs’ bioavailability and therapeutic effect on clinical application, these monotherapy-based nano-formulations still show poor progression in overcoming MDR. Herein, a “one stone and three birds” nanococktail (HA-HNRplex, 186 nm) integrated by a cocrystal@protein-anchoring strategy was purposed for triple-payload delivery, which paclitaxel (PTX)-disulfiram (DSF) cocrystal-like nanorods (NRs) were anchored with the basic protein drug Cytochrome c (Cyt C), followed by hyaluronic acid (HA) modification. In particular, NRs were utilized as carrier-like particles to synchronously deliver biomacromolecule Cyt C into tumor cells and then promote cell apoptosis. Of note, on A549/Taxol drug-resistant tumor-bearing mice, the HA-HNRplex with extraordinarily high encapsulation efficiency (PTX: 98.01%; DSF: 96.71%; Cyt C: ∼100%) demonstrated prolonged in vivo circulation and increased tumor-targeting accumulation, significantly reversing tumor drug resistance and improving therapeutic efficacy. Our mechanistic study indicated that HA-HNRplex induced the apoptosis of Taxol-resistant tumor cells through the signal axis P-gp/Cyt C/caspase 3. Collectively, this cocrystal@protein-anchoring nanococktail strategy offers a promising approach to improve the sensitivity of tumor cells to chemotherapeutic drugs and strengthen intractable drug-resistant oncotherapy.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2019
·Vol. 9
·期 3
·667-678
·
IF 3.111
Zhang Qian,Tian Xin,Cao Xiufeng
In this study, we developed an intravenously injectable, transferrin-functionalised microemulsion that simultaneously carries β-elemene and celastrol (called Tf-EC-MEs) for enhanced anti-lung cancer treatment and reduced systemic toxicity. These dual-drug-loaded Tf-EC-MEs not only displayed synergistic antiproliferative effects on cultured cells in vitro, but also showed enhanced efficacy in vivo via active tumour targeting. In preparatory experiments, we found that β-elemene was capable of being used as oil phase, which enhanced drug-loading efficiency and allowed the mass ratio of β-elemene and celastrol to be optimised. In cellular studies, Tf-EC-MEs exhibited significantly improved A549 cellular uptake compared with β-elemene+celastrol (conventional combination treatment) and EC-MEs (non-active targeted treatment), demonstrating remarkable synergistic antiproliferative effects and higher rates of cell apoptosis. In A549-bearing xenograft mouse tumour models, Tf-EC-MEs exhibited enhanced antitumour activity compared to all other treatments. More importantly, Tf-EC-MEs did not cause the obvious systemic toxicity commonly found with mono-celastrol treatment. Collectively, these findings suggest that Tf-EC-MEs are a promising strategy for the combination drug treatment of lung cancer.
研究领域:
药学
·
肿瘤学
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药物递送系统
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2018
·
IF 2.829
Xiaoran Li,Vasil M. Garamus,Na Li,Yabin Gong,Zhe Zhe,Zhenfen Tian,Aihua Zou
This study was aimed at preparing a highly dispersed and pH-sensitive mesoporous silica nanoparticles (MSNs) carrier via surface modification with polydopamine (PDA) and polyethylene glycol (PEG) i.e. [email protected] Small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) measurements suggested that hexagonally structured MSNs (type MCM-41) with the layer of PDA and PEG of thickness ∼20 nm were successfully prepared. Bovine serum protein (BSA) adsorption experiments showed that less protein was absorbed by [email protected] after the anchoring of PEG, which confirmed the stealth properties of prepared carriers. Doxorubicin hydrochloride (DOX) was used as the model drug to be encapsulated into [email protected] (DOX/ [email protected] ). The DOX/ [email protected] had relatively high entrapment efficiency and drug loading up to 94.2% and 31.4%, respectively. The in vitro release profile of DOX/ [email protected] exhibited pH-responsive and gradual drug release. Cytotoxicity assay showed that DOX/ [email protected] had comparable cytotoxicity to A549 cells compared to pure DOX. The intracellular distribution of DOX/ [email protected] was imaged using confocal laser scanning microscope. It points that PDA and PEG can play “gatekeeper” and stealth roles for MSNs as promising nanocarrier for cancer treatment.
研究领域:
纳米技术
·
药学
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材料科学
·
生物医学工程
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产品关联
DOI
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2022
·Vol. 31
·期 4
·605-616
·
IF 2.351
Shi Jing-Fang,Wu Ping,Li Han-Xiang,Wei Xiao-Yi,Jiang Zi-Hua
Annonaceous acetogenins are potent ubiquinone-linked NADH oxidase inhibitors and have potent anticancer activity. Their usage in the clinic is limited because of their significant toxicity to normal cells. To obtain novel low toxicity antitumoral prodrugs, squamocin and bullatacin were covalently linked to N -butoxycarbonyl protected glycine-proline dipeptide (Boc-Gly-Pro), which may be recognized and cleaved by fibroblast activation protein (FAP), a serine protease overexpressed on the surface of tumor-associated fibroblasts. Ten squamocin and bullatacin derivatives were synthesized by attaching Boc-Gly-Pro either directly or through 6-aminocaproic acid linker to a hydroxyl group of squamocin or bullatacin. All derivatives showed high potency to inhibit 4T1 breast cancer cell line growth in the sub-µM to µM range. Compound 8 was the most active (IC 50 0.30 μM) and displayed higher activity than squamocin. Most derivatives, however, display reduced potency by up to 50 folds compared to the parent drug. In the presence of FAP enzyme, the anticancer potency of compound 3 against A549, HeLa, HepG2 and MCF-7 cells was increased by up to eight folds. The data suggest that Boc-Gly-Pro-acetogenin prodrugs may show improved therapeutic potential of these acetogenins by reducing the drug doses and the toxic side effects.
Graphical abstract
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 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）