Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
Enzyme-responsive hydrogels have great potential in applications of controlled drug release, tissue engineering, etc. In this study, we reported on a supramolecular hydrogel that showed responses to two enzymes, phosp...Enzyme-responsive hydrogels have great potential in applications of controlled drug release, tissue engineering, etc. In this study, we reported on a supramolecular hydrogel that showed responses to two enzymes, phosphatase which was used to form the hydrogels and esterase which could trigger gelsol phase transitions. The gelation process and visco-elasticity property of the resulting gel, morphology of the nanostructures in hydrogel, and peptide conformation in the self-assembled nanostructure were characterized by theology, transmission electron microscope （TEM）, and circular dichroism （CD）, respectively. Potential application of the enzyme-responsive hydrogel in drug release was also demonstrated in this study. Though only one potential application of drug release was proved in this study, the responsive hydrogel system in this study might have potentials for the applications in fields of cell culture, controlled-drug release, etc.展开更多
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
基金This work was supported by National Natural Science Foundation of China （No. 20974054） and Tianjin MSTC （No. 11JCZDJC17200）.
文摘Enzyme-responsive hydrogels have great potential in applications of controlled drug release, tissue engineering, etc. In this study, we reported on a supramolecular hydrogel that showed responses to two enzymes, phosphatase which was used to form the hydrogels and esterase which could trigger gelsol phase transitions. The gelation process and visco-elasticity property of the resulting gel, morphology of the nanostructures in hydrogel, and peptide conformation in the self-assembled nanostructure were characterized by theology, transmission electron microscope （TEM）, and circular dichroism （CD）, respectively. Potential application of the enzyme-responsive hydrogel in drug release was also demonstrated in this study. Though only one potential application of drug release was proved in this study, the responsive hydrogel system in this study might have potentials for the applications in fields of cell culture, controlled-drug release, etc.
