Abstract:
:Notch pathway was found to be activated in most glioblastomas (GBMs), underlining the importance of Notch in formation and recurrence of GBM. In this study, a Notch inhibitory peptide, dominant negative MAML (dnMAML), was conjugated to elastin-like polypeptide (ELP) for tumor targeted delivery. ELP is a thermally responsive polypeptide that can be actively and passively targeted to the tumor site by localized application of hyperthermia. This complex was further modified with the addition of a cell penetrating peptide, SynB1, for improved cellular uptake and blood-brain barrier penetration. The SynB1-ELP1-dnMAML was examined for its cellular uptake, cytotoxicity, apoptosis, cell cycle inhibition and the inhibition of target genes' expression. SynB1-ELP1-dnMAML inhibited the growth of D54 and U251 cells by inducing apoptosis and cell cycle arrest, especially in the presence of hyperthermia. Hyperthermia increased overall uptake of the polypeptide by the cells and enhanced the resulting pharmacological effects of dnMAML, showing the inhibition of targets of Notch pathway such as Hes-1 and Hey-L. These results confirm that dnMAML is an effective Notch inhibitor and combination with ELP may allow thermal targeting of the SynB1-ELP1-dnMAML complex in cancer cells while avoiding the dangers of systemic Notch inhibition.
journal_name
J Drug Targetjournal_title
Journal of drug targetingauthors
Opačak-Bernardi T,Ryu JS,Raucher Ddoi
10.1080/1061186X.2017.1289537subject
Has Abstractpub_date
2017-07-01 00:00:00pages
523-531issue
6eissn
1061-186Xissn
1029-2330journal_volume
25pub_type
杂志文章abstract::The purpose of the study was to develop the liposomal formulations of TFu for oral and intravenous (i.v.) administration, clarify the biodistribution characteristics and in vivo pharmacokinetic behaviors of TFu-loaded liposomes. Four TFu-loaded liposomes of different sizes were prepared and characterized. The pharmaco...
journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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doi:10.3109/1061186X.2010.499460
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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doi:10.1080/10611860500383705
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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abstract::I125 radiolabelled HSA (HSA-I125) was utilised as a probe to quantify protein adsorption onto polystyrene (PS) and Poloxamine 908 coated PS (PS-908) particles. Upon ageing of the HSA-I125 a dramatic increase in the amount of protein adsorbed onto the two particle systems was observed. This phenomenon was not due to la...
journal_title:Journal of drug targeting
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doi:10.3109/10611869708995849
更新日期:1997-01-01 00:00:00
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journal_title:Journal of drug targeting
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doi:10.3109/10611869808997866
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abstract:BACKGROUND:Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. PURPOSE:El...
journal_title:Journal of drug targeting
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doi:10.3109/1061186X.2015.1076428
更新日期:2015-01-01 00:00:00
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journal_title:Journal of drug targeting
pub_type: 杂志文章,评审
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
pub_type: 杂志文章,评审
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更新日期:2004-02-01 00:00:00
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journal_title:Journal of drug targeting
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doi:10.1080/1061186X.2016.1200588
更新日期:2017-01-01 00:00:00
abstract::Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone com...
journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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更新日期:2019-02-01 00:00:00
abstract::Cyclodextrins (CDs) are macrocyclic oligosaccharides composed of α(1,4)-linked glucopyranose subunits. These molecules possess a cage-like supramolecular structure, comparable with the structures of crown ethers, cryptands, spherands, cyclophanes, or calixarenes. However, it took 50 years to establish the molecular st...
journal_title:Journal of drug targeting
pub_type: 杂志文章,评审
doi:10.3109/10611861003622552
更新日期:2010-11-01 00:00:00
abstract::The phenomenal advances in pharmaceutical sciences over the last few decades have led to the development of new therapeutics like peptides, proteins, RNAs, DNAs and highly potent small molecules. Fruitful applications of these therapeutics have been challenged by several anatomical and physiological barriers that limi...
journal_title:Journal of drug targeting
pub_type: 杂志文章,评审
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更新日期:2018-01-01 00:00:00