Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delive...Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity.Moreover,for the intracellularly acted proteins,cell membrane as a primary barrier hinders the transmembrane delivery of proteins.The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes.We herein develop a proteasemanipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins.The embedded polymeric nanogels(CytoC/aNGs)preserve activity of cytochrome c(CytoC)that is an intracellular activator for cell apoptosis as a model protein against proteolysis,and do not affect the gelation properties of the protease-catalysis assembled hydrogels.The injectable hydrogel(CytoC/aNGs/Gel)serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs.The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site,cytoplasm,resulting in favorable apoptosis-inducing and cytotoxic effects.We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.展开更多
As a magical creature,chameleon is good at adjusting body color according to the change of environment,which is good for capturing prey or protecting itself from danger.Research has shown that chameleon can adjust the...As a magical creature,chameleon is good at adjusting body color according to the change of environment,which is good for capturing prey or protecting itself from danger.Research has shown that chameleon can adjust the nanocrystals on the surface of the skin to change the refraction of light,thus showing different colors[1].展开更多
基金supported by the National Key Research and Development Program of China(No.2019YFA0905200)the National Natural Science Foundation of China(No.81971730,No.81503012)+1 种基金the Natural Science Foundation of Jiangsu Province of China for Excellent Young Scholars(No.BK20190084)the Young Elite Scientists Sponsorship Program by CAST(China)
文摘Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity.Moreover,for the intracellularly acted proteins,cell membrane as a primary barrier hinders the transmembrane delivery of proteins.The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes.We herein develop a proteasemanipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins.The embedded polymeric nanogels(CytoC/aNGs)preserve activity of cytochrome c(CytoC)that is an intracellular activator for cell apoptosis as a model protein against proteolysis,and do not affect the gelation properties of the protease-catalysis assembled hydrogels.The injectable hydrogel(CytoC/aNGs/Gel)serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs.The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site,cytoplasm,resulting in favorable apoptosis-inducing and cytotoxic effects.We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.
基金the National Key R&D Program of China (2019YFA09005200)the National Natural Science Foundation of China (81673321)+1 种基金the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture (XTC1812)the Special Funds for the Introduction of Talents of Nanjing Tech University (39828122)。
文摘As a magical creature,chameleon is good at adjusting body color according to the change of environment,which is good for capturing prey or protecting itself from danger.Research has shown that chameleon can adjust the nanocrystals on the surface of the skin to change the refraction of light,thus showing different colors[1].
