title: Nonspecific Colloidal-Type Interaction Explains Size-Dependent Specific Binding of Membrane-Targeted Nanoparticles.
abstract: Emerging biomedical applications such as molecular imaging and drug delivery often require directed binding of nanoparticles to cell-membrane receptors. The specific apparent affinity of such ligand-functionalized particles is size-dependent, an observation so far solely attributed to multivalent receptor-ligand interaction. We question the universality of this explanation by demonstrating that the binding kinetics also depends on weak, attractive colloidal-type interaction between nanoparticles and a lipid membrane. Applying label-free single-particle imaging, we correlate binding of nanoparticles targeted to a cell-mimetic lipid membrane with the distribution of nontargeted particles freely diffusing close to the membrane interface. This analysis shows that already a weak, kBT-scale attraction present between 50 nm gold nanoparticles and the membrane renders these particles an order of magnitude higher avidity compared to 20 nm particles. A stronger emphasis on nonspecific particle-membrane interaction might thus be required to accurately predict nanoparticle targeting and other similar processes such as cellular uptake of exosomes and viruses.
authors: Department of Physics, Chalmers University of Technology , Gothenburg 412 96, Sweden.|Department of Nanobiotechnology, University of Natural Resources and Life Sciences , Vienna 1190, Austria.
authors: Anders
authors: A
authors: Lundgren
authors: Department of Physics, Chalmers University of Technology , Gothenburg 412 96, Sweden.
authors: Björn
authors: B
authors: Agnarsson
authors: Department of Nanobiotechnology, University of Natural Resources and Life Sciences , Vienna 1190, Austria.
authors: Ronald
authors: R
authors: Zirbs
authors: Department of Physics, Chalmers University of Technology , Gothenburg 412 96, Sweden.|Boreskov Institute of Catalysis, Russian Academy of Sciences , Novosibirsk 630090, Russia.
authors: Vladimir P
authors: VP
authors: Zhdanov
authors: Department of Nanobiotechnology, University of Natural Resources and Life Sciences , Vienna 1190, Austria.
authors: Erik
authors: E
authors: Reimhult
authors: Department of Physics, Chalmers University of Technology , Gothenburg 412 96, Sweden.
authors: Fredrik
authors: F
authors: Höök
mesh_terms: D002462:Cell Membrane; D016503:Drug Delivery Systems; D006046:Gold; D008024:Ligands; D053768:Metal Nanoparticles; D053758:Nanoparticles; D010316:Particle Size; D011485:Protein Binding; D014780:Viruses / Q000187:drug effects
chemical_list: D008024:Ligands; D006046:Gold
keywords: DLVO interaction; light-scattering; lipid−membrane interaction; quartz crystal microbalance; single-particle imaging; targeted nanoparticles