A Nano-detector For Enhancing Cell Recognition Of Nickel Ion

Polymers play an important role in the life activities.The polymers,no matter how their constituents are active or not,are likely to play biological effects when combined with the cells via the nano-bio interface.The interaction between polymers and cells is a precise and complex process,and the binding ways of multivalent ligands and receptors activate specific signaling pathways,which could cause the unique biological response,So it is a very challenge and significantly Nano-biomedical prospect that the artificially controlled binding polymers with cells to control cell response via these ways.The heavy metal ions could damage the intracellular proteins,nucleic acids and other functional molecules to cause the damage of organisms,when accumulated to a certain extent in vivo.However,cells have not specific response mechanism to be sense to the heavy metal ions to make the defense reaction,due to no existence of high heavy metal ions caused by modern industry in the early evolution.In this paper,we take,for example,nickel ions(Ni2+),and base on its chelation to design a multivalent ligand that coordinate with Ni2+:histidine(His)modified hyaluronic acid(HA).After Ni2+ chelation,histidine modified hyaluronic acid(Ni2+-His-HA)could form nanoparticles with a certain size,which could affected the aggregation of CD44 on the cell surface and further mediated cell responses.We detected the expression levels of related cytokines by ELISA assay:Compared with the Ni2+ stimulation,Ni2+-His-HA nanoparticles could make primary peritoneal macrophages secrete more than 10 times tumor necrosis factor-a(TNF-a).Meanwhile,transmission electron microscopy demonstrated that Ni2+-His-HA could form a certain size of nanoparticles,and the immunofluorescence tests shown that CD44 could be organized into nanoscale clusters.we validated that cells can response to Ni2+-His-HA nanoparticles at the genetic level by Luciferase assay.Together,these findings demonstrated that the nano-polymer(His-HA)may be a powerful detector for cells being specific sense to Ni2+.