Neural crest(NC)is the primitive neural structure in embryonic stage,which develops from ectodermal neural plate cells and epithelial cells.When the neural fold forms into neural tube,neural crest also forms a cord li...Neural crest(NC)is the primitive neural structure in embryonic stage,which develops from ectodermal neural plate cells and epithelial cells.When the neural fold forms into neural tube,neural crest also forms a cord like structure above the neural tube and below the ectoderm.Neural crest cells(NCC)have strong migration and proliferation abilities.A number of tissue cells differentiate from neural crest cells,such as melanocytes,central and peripheral neurons,glial cells,craniofacial cells,osteoblasts,chondrocytes and smooth muscle cells.The migration and differentiation of neural crest cells are regulated by a gene network where a variety of genes,transcriptional factors,signal pathways and growth factors are involved.展开更多
Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries great...Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue.Here,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this barrier.As a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging agents.All compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB.The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.展开更多
文摘Neural crest(NC)is the primitive neural structure in embryonic stage,which develops from ectodermal neural plate cells and epithelial cells.When the neural fold forms into neural tube,neural crest also forms a cord like structure above the neural tube and below the ectoderm.Neural crest cells(NCC)have strong migration and proliferation abilities.A number of tissue cells differentiate from neural crest cells,such as melanocytes,central and peripheral neurons,glial cells,craniofacial cells,osteoblasts,chondrocytes and smooth muscle cells.The migration and differentiation of neural crest cells are regulated by a gene network where a variety of genes,transcriptional factors,signal pathways and growth factors are involved.
基金supported by following funds:National Key Research and Development project of China(2020YFC20052003,to S.Y.)National Science and Technology Major Project for Major New Drugs Innovation and Development under grant(2018ZX09711003,to W.Z.)+3 种基金Key International(Regional)Joint Research Program of National Nature Science Foundation of China(81820108009,to S.Y.)National Nature Science Foundation of China(81800916 to X.S.,31471299 and 81522046 to J.L.)The Nature Science Foundation of Xuzhou(KC20177 to X.S.)Jiangsu Provincial University Fund(19KJA560002 to X.S.).
文摘Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue.Here,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this barrier.As a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging agents.All compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB.The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.
