title: Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface.
abstract: Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona can 'screen' the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.
authors: Centre for BioNano Interactions, School of Chemistry and Chemical Biology, UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Anna
authors: A
authors: Salvati
authors: Andrzej S
authors: AS
authors: Pitek
authors: Marco P
authors: MP
authors: Monopoli
authors: Kanlaya
authors: K
authors: Prapainop
authors: Francesca Baldelli
authors: FB
authors: Bombelli
authors: Delyan R
authors: DR
authors: Hristov
authors: Philip M
authors: PM
authors: Kelly
authors: Christoffer
authors: C
authors: Åberg
authors: Eugene
authors: E
authors: Mahon
authors: Kenneth A
authors: KA
authors: Dawson
mesh_terms: D000327:Adsorption; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002942:Circular Dichroism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011506:Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011990:Receptors, Transferrin / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D014168:Transferrin / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D000906:Antibodies; D011506:Proteins; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D014168:Transferrin; D012822:Silicon Dioxide