title: Influence of targeting ligand flexibility on receptor binding of particulate drug delivery systems.
abstract: Receptor-mediated drug targeting via nanoengineered particulate delivery systems is an emerging field. However, little is known about how such magic bullets should be assembled to yield optimal targeting efficiency. Here we investigated the influence of targeting ligand flexibility on binding of ligand-coated microparticles to cell surface receptors. Using the ganglioside G(M1)-binding B subunit of cholera toxin as ligand and fluorescent microparticles as a model delivery system, conjugates with different numbers of linkages between ligand and particle were prepared and tested for their efficiency to bind to live fibroblast monolayers. Our results show that multiple bonds between ligand and particle reduce the targeting rate by up to 50% compared to constructs where ligands are attached via single aliphatic chains. Thus, for maximum performance, targeted particulate drug delivery systems should be assembled such that ligands are attached via single sigma bonds only, allowing the ligand molecules to adopt an optimal binding conformation.
authors: Institut für Infektiologie, Zentrum für Molekularbiologie der Entzündung, von-Esmarch-Strasse 56, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
authors: Verena
authors: V
authors: Olivier
authors: Iris
authors: I
authors: Meisen
authors: Barbara
authors: B
authors: Meckelein
authors: Timothy R
authors: TR
authors: Hirst
authors: Jasna
authors: J
authors: Peter-Katalinic
authors: M Alexander
authors: MA
authors: Schmidt
authors: Andreas
authors: A
authors: Frey
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019921:Biotinylation; D002772:Cholera Toxin / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000378:metabolism; D005456:Fluorescent Dyes; D005677:G(M1) Ganglioside / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D005677:G(M1) Ganglioside; D002772:Cholera Toxin