DALTON TRANSACTIONS
·
2013
·Vol. 42
·期 27
·9852-9861
·
IF 3.806
Yuan Wu,Dongmei Yang,Xiaojiao Kang,Ping'an Ma,Shanshan Huang,Yang Zhang,Chunxia Li,Jun Lin
Multifunctional nanocomposites integrating mesoporous and luminescence properties into a single entity are synthesized via a facile and effective approach. Oleic acid capped β-NaYF4:Ce3+/Tb3+ nanoparticles (NPs) are transferred into aqueous solution by cetyltrimethylammonium bromide (CTAB) surfactants, and further encapsulated with uniform mesoporous silica shell followed by the surface modification with poly(ethylene glycol) (PEG), leading to the formation of water-dispersible and biocompatible core–shell structured β-NaYF4:Ce3+/Tb3+@mSiO2-PEG (denoted as NPs@mSiO2-PEG) nanospheres. The as-synthesized nanospheres show a typical mesoporous structure and a green emission under UV irradiation. Doxorubicin hydrochloride (DOX), a widely used anti-cancer drug, is used as a model drug to evaluate the loading and controlled release behaviors of the NPs@mSiO2-PEG in phosphoric acidic buffer solutions (PBS) at different pH values (pH = 7.4 and 5.0). The composite carriers provide a pH-sensitive drug release pattern and the drug releases faster under lower pH value. The endocytosis process of fluorescein isothiocyanate (FITC)-labelled nanospheres is characterized using flow cytometry and confocal laser scanning microscopy (CLSM) against A549 cells. The in vitro cytotoxic effect against A549 cells of the DOX-loaded carriers is investigated in detail. In addition, the extent of drug release can be monitored by the variation of photoluminescence (PL) intensity of β-NaYF4:Ce3+/Tb3+. Considering the good biocompatibility and pH-dependent drug release pattern, such core–shell structured luminescent NPs@mSiO2-PEG nanospheres have potential applications in controlled drug delivery.
研究领域:
生物材料
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
POLYMER
·
2013
·
IF 3.379
Fuli Feng,Rongrong Li,Qingyun Zhang,Yinsong Wang,Xiaoying Yang,Hongquan Duan,Xinlin Yang
The reduction-triggered degradable poly(methacrylic acid- co - N,N -bis(acryloyl)cystamine)/polyethyleneimine (P(MAA- co -BAC)/PEI) microcapsules were prepared by distillation–precipitation polymerization for delivery of anti-cancer drug and gene. N,N- bis(acryloyl)cystamine (BAC) as a crosslinker containing a disulfide bond can be triggered by reductive agents, such as glutathione (GSH) and dithiothreitol (DTT), to endow the functional microcapsules with reduction-triggered drug release. The P(MAA- co -BAC)/PEI microcapsules were characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectra (FT-IR), laser particle size analyzer and elemental analysis . The degradable behavior of microcapsules was investigated by analysis of UV-vis spectroscopy. The controlled drug release behavior for P(MAA- co- BAC)/PEI microcapsules was strongly dependent on the absence/presence of GSH and the pH values with doxorubicin hydrochloride (DOX) as a model drug molecule. The in vitro gene transfection ability was evaluated by Hela cells with the transfection of plasmid DNA (pDNA) encoded with green fluorescent protein (GFP) and the transfection efficiency was determined by confocal fluorescence microscopy . Furthermore, the cytotoxicities of (P(MAA- co -BAC)/PEI) microcapsules before and after loading of DOX were assessed via WST-1 assay. The P(MAA- co -BAC)/PEI microcapsules provide the potential novel vectors for delivery of drugs and genes, promising for future applications in anticancer drug and gene combined therapy.
研究领域:
生物医学工程
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOCONJUGATE CHEMISTRY
·
2015
·
IF 4.513
Mingzhi Wang,Chuncai Zhou,Jing Chen,Yufen Xiao,Jianzhong Du
Cancer patients after chemotherapy may also suffer bacterial attack due to badly decreased immunity. Although with high bacterial efficacy, conventional antibiotics are prone to inducement of drug resistance and may be not suitable for some cancer patients. In contrast, antibacterial peptides are highly effective in inhibiting bacteria without inducing resistance in pathogens. Presented in this article is a novel kind of highly effective antibacterial peptide-based biocompatible and biodegradable block copolymer vesicle. The copolymer is poly(ε-caprolactone)-block-poly[phenylalanine-stat-lysine-stat-(lysine-folic acid)] [PCL19-b-poly[Phe12-stat-Lys9-stat-(Lys-FA)6]], which can self-assemble into vesicles in aqueous solution. The biocompatible and biodegradable PCL forms the vesicle membrane, whereas the poly[Phe12-stat-Lys9-stat-(Lys-FA)6] block constitutes the vesicle coronas. Compared to the individual polymer chains, the vesicles showed enhanced antibacterial activities against both Gram-positive and Gram-negative bacteria (16 μg mL–1) due to the locally concentrated antibacterial poly[Phe12-stat-Lys9-stat-(Lys-FA)6] coronas, which may avoid the inducement of antibiotic-resistant bacteria and side effects of multidrug interactions. Furthermore, folic acid is introduced into the vesicle coronas for potential further applications such as cancer-targeted drug delivery. Moreover, the amino groups can be further functionalized when necessary. This low cytotoxic, biocompatible, biodegradable, and antibacterial vesicle (without antibiotic resistance) may benefit patients after tumor surgery because it is highly anti-inflammatory, and it is possible to deliver the anticancer drug to tumor cells simultaneously.
研究领域:
生物材料
·
医学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 35
·21837-21847
·
IF 3.108
Huixiang Zhong,Liuyang Xuan,Dandan Wang,Jianhua Zhou,Yan Li,Qing Jiang
Lung cancer bone metastases usually involve multiple interactions between cancer cells and host organs. To mimic such a structure, a cell co-culture micropattern of A549 lung cancer cells and osteoblast cells (A549/OB) was developed using a μ-eraser strategy for anti-cancer drug evaluation and also understanding cell–cell communication. When applying the μ-eraser strategy, a PDMS stamp was pressed to induce cell lysis. Hence, the minimum pressure required to induce cell lysis was first quantified. Then the pressure and pressing time for the micropatterning process were optimized to obtain cell micropatterns of high fidelity and repeatability. For different types of cells (A549 and human mesenchymal stem cells) and different substrates (TCP and PLGA nanofiber sheets), the optimized pressure was also different (i.e., for A549 on TCP, a pressure of 24.5 kPa was pressed for 10 s). According to a live/dead assay and Alamar Blue assay, cell viability and proliferation potential were not affected by the micropatterning process. There were several advantages for the μ-eraser strategy: substrates were not pre-treated; cell micropatterns mainly relied on the pattern of the PDMS stamp along with the micropatterning process; cells in the micropattern were not restricted in specified regions. Thus the A549/OB co-culture micropattern on TCP was used to evaluate the efficacy of a therapeutic agent (doxorubicin). In the co-culture micropattern, the efficacy of doxorubicin decreased when the expression of ALP in OB was elevated. The co-culture micropattern model showed the potential to be used for new anti-cancer drug development.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2015
·
IF 0.633
Haidong Liu,Yongfeng Lv,Yuan Li,Jin Cai,Junqing Chen,Yu Qin,Min Ji
A convenient route for the synthesis of a third-generation epidermal growth factor receptor inhibitor, mereletinib (AZD9291) using starting materials that are commercially available has been achieved through reactions that are readily conducted under mild conditions. Importantly, a 5 g scale synthesis was also accomplished and this method could therefore be useful in the synthesis of similar drugs.
研究领域:
药物化学
·
有机合成
·
肿瘤学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 35
·18171-18177
·
IF 3.708
Shuying Yu,Wenhua Yang,Sheng Chen,Mengjie Chen,Yezhuo Liu,Zhengzhong Shao,Xin Chen
Silk protein is a very promising biomedical material due to its renewability, nontoxicity, biocompatibility, and biodegradability. In this communication, we report our attempt to use regenerated silk fibroin (RSF) as a drug-carrier to encapsulate hydrophilic anti-cancer drug floxuridine (FUDR). The FUDR-loaded RSF nanospheres with the average sizes ranging from 210 to 510 nm are prepared by using a facile and clean method developed in this laboratory previously based on the self-assembly of silk protein. The maximum drug loading is about 6.8% and the release time of such a kind of FUDR-loaded RSF nanospheres is more than 2 days. The FUDR-loaded RSF nanospheres are found to be able to adhere to the Hela cells easily. The FUDR loaded in the RSF nanospheres exhibits the similar curative effect to kill or inhibit Hela cells to the free FUDR. All these results imply that such a kind of biomacromolecule based anti-cancer drug nanocarrier has a great potential for the lymphatic chemotherapy in clinical applications.
研究领域:
生物医学材料
·
肿瘤学
·
药剂学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 19
·11711
·
IF 6.208
Huan-Chau Lin,Ferry Saputra,Gilbert Audira,Yu-Heng Lai,Marri Jmelou M. Roldan,Honeymae C. Alos,Charlaine A. Aventurado,Ross D. Vasquez,Guan-Jhe Tsai,Ken-Hong Lim,Chung-Der Hsiao
BCR-ABL, a fusion protein kinase, is a druggable target exclusively expressed in patients with chronic myeloid leukemia (CML). Several anti-leukemia medicines targeting this protein have been developed in recent years. However, therapeutic options are limited for CML patients bearing multiple BCR-ABL1 mutations. Ponatinib (PON), a potent tyrosinase inhibitor, was one of the approved drugs for managing BCR-ABL1 T315I mutant disease. However, treatment of patients with PON reported severe side effects related to cardiovascular events. Asciminib (ASC) was the first allosteric inhibitor approved to target the myristoyl pocket of BCR-ABL protein to inhibit protein activity. The different mechanism of inhibition opens the possibility of co-exposure with both medicines. Reports on cardiovascular side effects due to the combination use of PON + ASC in pre-clinical and clinical studies are minimal. Thus, this study aimed to observe the potential cardiovascular-related side effect after co-exposure to ASC and PON using zebrafish as an animal model. In this study, zebrafish were acutely exposed to both compounds. The cardiovascular physiology parameters and gene expression related to cardiovascular development were evaluated. We demonstrate that combining ASC with PON at no observed effect concentration (NOEC) did not cause any significant change in the cardiac performance parameter in zebrafish. However, a significant increase innkx2.5expression level and a substantial decrease in blood flow velocity were recorded, suggesting that combining these compounds at NOEC can cause mild cardiovascular-related side effects.Keywords:zebrafish;anti-cancer drug;asciminib;ponatinib;cardiovascular toxicity;molecular docking
研究领域:
药理学
·
毒理学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 5
·1414
·
IF 5.4
Ruizhuo Ouyang,Jinyao Liu,Shen Wang,Weilun Zhang,Kai Feng,Conghao Liu,Baolin Liu,Yuqing Miao,Shuang Zhou
In order to develop new anti-cancer drugs more efficiently and reduce side effects based on active drug targets, the virtual drug screening was carried out through the target of G-quadruplexes and 23 hit compounds were, thus, screened out as potential anticancer drugs. Six classical G-quadruplex complexes were introduced as query molecules, and the three-dimensional similarity of molecules was calculated by shape feature similarity (SHAFTS) method so as to reduce the range of potential compounds. Afterwards, the molecular docking technology was utilized to perform the final screening followed by the exploration of the binding between each compound and four different structures of G-quadruplex. In order to verify the anticancer activity of the selected compounds, compounds 1, 6 and 7 were chosen to treat A549 cells in vitro, the lung cancer epithelial cells, for further exploring their anticancer activity. These three compounds were found to be of good characteristics in the treatment of cancer, which revealed the great application prospect of the virtual screening method in developing new drugs.
研究领域:
药理学
·
生物信息学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2011
·
IF 3.044
Jundong Zhu,Zhichao Zhou,Cuihong Yang,Deling Kong,Ying Wan,Zheng Wang
Folate (FA)-conjugated star-shaped copolymer was prepared as a targeted carrier for anticancer drug delivery by ring-opening polymerization of L -lactide using pentaerythritol (PTL) as an initiator, followed by conjugation with methoxy poly(ethylene glycol) (MPEG) and FA-poly(ethylene glycol) (FA-PEG). The resulting amphiphilic star-shaped copolymer was shaped into drug-loaded micelles, and the achieved micelles had an average size of around 146 nm in diameter. It was found that the sustained release time of model drug (indomethacin, IMC) from some selected micelles could reach around 40 h. In comparison with linear poly( L -lactic acid)-block-methoxy poly(ethylene glycol) copolymer (PLA-MPEG), the stability of the star-shaped pentaerythritol- co -poly( L -lactic acid)-block-[methoxy poly(ethylene glycol) and FA-poly(ethylene glycol)] (PTL-PLA-MPEG/PEG-FA) micelle was significantly improved because of the lower critical micelle concentration (CMC). The specificity of PTL-PLA-MPEG/PEG-FA targeting cancer cells was demonstrated by intracellular uptake of PTL-PLA-MPEG/PEG-FA and PTL-PLA-MPEG using HeLa human cervical cancer cells. After 2 h in vitro incubation, a significant intracellular uptake for PTL-PLA-MPEG/PEG-FA over PTL-PLA-MPEG was observed by using inverted fluorescence microscope and flow cytometry. These results suggested that PTL-PLA-MPEG/PEG-FA polymeric micelle could be a potentially useful carrier for delivering selected drugs to FA-receptor positive cancer cells. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
研究领域:
生物材料
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2012
·Vol. 18
·期 49
·15676-15682
·
IF 5.925
Xiao-Jiao Kang,Yun-Lu Dai,Ping-An Ma,Dong-Mei Yang,Chun-Xia Li,Zhi-Yao Hou,Zi-Yong Cheng,Jun Lin
Graphical Dual response : Monodisperse poly(acrylic acid)-modified Fe 3 O 4 (PAA@Fe 3 O 4 ) hybrid microspheres with dual responses (magnetic field and pH) were successfully fabricated (see figure). The drug release behavior was strongly dependent on pH value due to the unique properties of PAA. Furthermore, doxorubicin (DOX)-loaded PAA@Fe 3 O 4 composites show an enhanced magnetically guided anticancer effect. Monodisperse poly(acrylic acid)-modified Fe 3 O 4 (PAA@Fe 3 O 4 ) hybrid microspheres with dual responses (magnetic field and pH) were successfully fabricated. The PAA polymer was encapsulated into the inner cavity of Fe 3 O 4 hollow spheres by a vacuum-casting route and photo-initiated polymerization. TEM images show that the samples consist of monodisperse porous spheres with a diameter around 200 nm. The Fe 3 O 4 spheres, after modification with the PAA polymer, still possess enough space to hold guest molecules. We selected doxorubicin (DOX) as a model drug to investigate the drug loading and release behavior of as-prepared composites. The release of DOX molecules was strongly dependent on the pH value due to the unique property of PAA. The HeLa cell-uptake process of DOX-loaded PAA@Fe 3 O 4 was observed by confocal laser scanning microscopy (CLSM). After being incubated with HeLa cells under magnet magnetically guided conditions, the cytotoxtic effects of DOX-loaded PAA@Fe 3 O 4 increased. These results indicate that pH-responsive magnetic PAA@Fe 3 O 4 spheres have the potential to be used as anticancer drug carriers.
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Zhe Zhou,Jing Long,Yuan Wang,YaYun Li,Xu Zhang,Ling Tang,Qi Chang,Zhuo Chen,GaoYun Hu,Shuo Hu,QianBin Li,Cong Peng,Xiang Chen
CD147 is a transmembrane glycoprotein and a member of immunoglobulin superfamily, is strongly expressed in melanoma cells. CD147 has a pivotal role in tumor development. Therefore, it is a potential drug target for melanoma. In this article, we report the discovery of the first CD147 protein proteolysis targeting chimeras (PROTACs) derived from the natural product pseudolaric acid B (PAB). The representative compound 6a effectively induced degradation of CD147 and inhibited melanoma cells in vitro and in vivo. 6a could be used as the novel type of anticancer agent or as a part of the molecular biology research toolkit used in the gain-of-function study of the dynamic roles of CD147 in cancer networks.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Horticulture Research
·
2021
·
IF 6.793
Hao Xiaolong,Xie Chenhong,Ruan Qingyan,Zhang Xichen,Wu Chao,Han Bing,Qian Jun,Zhou Wei,Nützmann Hans-Wilhelm,Kai Guoyin
The limited bioavailability of plant-derived natural products with anticancer activity poses major challenges to the pharmaceutical industry. An example of this is camptothecin, a monoterpene indole alkaloid with potent anticancer activity that is extracted at very low concentrations from woody plants. Recently, camptothecin biosynthesis has been shown to become biotechnologically amenable in hairy-root systems of the natural producer Ophiorrhiza pumila. Here, time-course expression and metabolite analyses were performed to identify novel transcriptional regulators of camptothecin biosynthesis in O. pumila. It is shown here that camptothecin production increased over cultivation time and that the expression pattern of the WRKY transcription factor encoding gene OpWRKY2 is closely correlated with camptothecin accumulation. Overexpression of OpWRKY2 led to a more than three-fold increase in camptothecin levels. Accordingly, silencing of OpWRKY2 correlated with decreased camptothecin levels in the plant. Further detailed molecular characterization by electrophoretic mobility shift, yeast one-hybrid and dual-luciferase assays showed that OpWRKY2 directly binds and activates the central camptothecin pathway gene OpTDC. Taken together, the results of this study demonstrate that OpWRKY2 acts as a direct positive regulator of camptothecin biosynthesis. As such, a feasible strategy for the over-accumulation of camptothecin in a biotechnologically amenable system is presented.
研究领域:
植物生物技术
·
分子生物学
·
药理学
✓ 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）