Nanoparticles internalization through HIP-55-dependent clathrin endocytosis pathway

【作者】 关开行； 刘凯； 姜允奇； 边经纬； 高阳； 董尔丹； 李子健；

【机构】 北京大学第三医院；

【摘要】 Nanoparticles are promising tools for biomedicine.Many nanoparticles need to be internalized to function.Clathrin-mediated endocytosis is one of the most important mechanisms for nanoparticles internalization.However,the regulatory mechanism of clathrin-mediated nanoparticles endocytosis is still unclear.Here,we report adapter protein HIP-55 regulates clathrin-mediated nanoparticles endocytosis.CdSe/ZnS quantum dots(QDs),a typical nanoparticle,enter cells through HIP-55-dependent clathrin endocytosis pathway.Both pharmacological inhibitor and genetic intervention demonstrate QDs enter cells through clathrin-mediated endocytosis.HIP-55 can interact with clathrin and promote the clathrin-mediated QDs endocytosis.Furthermore,the HIP-55 ΔADF which is defective in F-actin binding,fails to promote QDs endocytosis,indicating HIP-55 promotes clathrin-mediated QDs endocytosis depending on interaction with F-actin.In vivo,HIP-55 knockout also inhibits QDs endocytosis.These findings reveal HIP-55 acts as an intrinsic regulator for clathrin-mediated nanoparticles endocytosis,providing a new insight into the nanoparticles internalization and a new strategy for nanodrugs enrichment in target cells.更多还原

【Abstract】 Nanoparticles are promising tools for biomedicine.Many nanoparticles need to be internalized to function.Clathrin-mediated endocytosis is one of the most important mechanisms for nanoparticles internalization.However,the regulatory mechanism of clathrin-mediated nanoparticles endocytosis is still unclear.Here,we report adapter protein HIP-55 regulates clathrin-mediated nanoparticles endocytosis.CdSe/ZnS quantum dots(QDs),a typical nanoparticle,enter cells through HIP-55-dependent clathrin endocytosis pathway.Both pharmacological inhibitor and genetic intervention demonstrate QDs enter cells through clathrin-mediated endocytosis.HIP-55 can interact with clathrin and promote the clathrin-mediated QDs endocytosis.Furthermore,the HIP-55 ΔADF which is defective in F-actin binding,fails to promote QDs endocytosis,indicating HIP-55 promotes clathrin-mediated QDs endocytosis depending on interaction with F-actin.In vivo,HIP-55 knockout also inhibits QDs endocytosis.These findings reveal HIP-55 acts as an intrinsic regulator for clathrin-mediated nanoparticles endocytosis,providing a new insight into the nanoparticles internalization and a new strategy for nanodrugs enrichment in target cells.更多还原