Multivalent display and receptor-mediated endocytosis of transferrin on virus-like particles.

摘要: The structurally regular and stable self-assembled capsids derived from viruses can be used as scaffolds for the display of multiple copies cell- tissue-targeting molecules therapeutic agents in a convenient well-defined manner. human iron-transfer protein transferrin, high affinity ligand receptors upregulated variety cancers, has been arrayed on exterior surface capsid bacteriophage Qbeta. Selective oxidation sialic acid residues glycan chains transferrin was followed by introduction terminal alkyne functionality through an oxime linkage. Attachment to azide-functionalized Qbeta particles orientation allowing access receptor binding site accomplished Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Transferrin conjugation allowed specific recognition cellular internalization clathrin-mediated endocytosis, determined fluorescence microscopy cells expressing GFP-labeled clathrin light chains. By testing bearing different numbers molecules, it demonstrated that uptake proportional density, but inhibited equivalent concentrations free transferrin. These results suggest cell targeting with improved local concentration (avidity) effects.