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Potent tumor targeting drug release system comprising MMP-2 specific peptide fragment with self-assembling characteristics
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Potent tumor targeting drug release system comprising MMP-2 specific peptide fragment with self-assembling characteristics
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Journal Article
Potent tumor targeting drug release system comprising MMP-2 specific peptide fragment with self-assembling characteristics
2014
Overview
Self-assembling peptides are capable of forming a complex containing a cavity where cytotoxic agents can be wrapped in a self-assembling manner. These complexes are beneficial for improving the pharmacological properties and pharmacokinetics of cytotoxic agents, such as doxorubicin and paclitaxel. In the present study, this self-assembling feature was successfully integrated into a hexapeptide with matrix metalloproteinase (MMP)-2 specific targeting activity, producing a supramolecule possessing controlled drug release characteristics. The MMP-2 specific substrate fragment, PVGLIG, makes this supramolecule disassociate in the presence of MMP-2, and this system is considered to be a powerful tool for the treatment of tumors with high expression of MMP-2 or tumor metastasis. Our findings show that this modified self-assembling peptide with the PVGLIG fragment was able to significantly enhance specificity against HT1080 cells, a tumor cell line with high expression of MMP-2. In addition, residence time of the complex in blood was prolonged since paclitaxel was wrapped into the supramolecule. Our results suggest that the modified MMP-2 specific substrate, SAMTA7, could act as a controlled and sustained drug carrier for treatment of tumors with high expression of MMP-2 and for tumor metastasis.
Publisher
Dove Medical Press Limited,Taylor & Francis Ltd,Dove Medical Press
Subject
/ Animals
/ Cancer
/ Cell Proliferation - drug effects
/ Female
/ Humans
/ Kinases
/ Matrix Metalloproteinase 2 - metabolism
/ Matrix Metalloproteinase Inhibitors - chemical synthesis
/ Matrix Metalloproteinase Inhibitors - chemistry
/ Matrix Metalloproteinase Inhibitors - pharmacology
/ Mice
/ Molecular Dynamics Simulation
/ Peptide Fragments - chemical synthesis
/ Peptide Fragments - chemistry
/ Peptide Fragments - pharmacology
/ Peptides
/ Structure-Activity Relationship
/ Tumors
