title: Receptor-mediated targeting of magnetic nanoparticles using insulin as a surface ligand to prevent endocytosis.
abstract: Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging contrast agents or in drug delivery applications. Tissue and cell-specific drug targeting by these nanoparticles can be achieved by employing nanoparticle coatings or carrier-drug conjugates that contain a ligand recognized by a receptor on the target cell. In this study, superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared and coupled to insulin for their targeting to cell expressed surface receptors and thereby preventing the endocytosis. The influence of these nanoparticles on human fibroblasts is studied using various techniques to observe cell-nanoparticle interaction that includes light, scanning, and transmission electron microscopy studies. The derivatization of the nanoparticle surface with insulin-induced alterations in cell behavior that were distinct from the underivatized nanoparticles suggests that cell response can be directed via specifically engineered particle surfaces. The results from cell culture studies showed that the uncoated particles were internalized by the fibroblasts due to endocytosis, which resulted in disruption of the cell membrane. In contradiction, insulin-coated nanoparticles attached to the cell membrane, most likely to the cell-expressed surface receptors, and were not endocytosed. The presence of insulin on the surface of the nanoparticles caused an apparent increase in cell proliferation and viability. One major problem with uncoated nanoparticles has been the endocytosis of particles leading to irreversible entry. These results provide a route to prevent this problem. The derivatized nanoparticles show high affinity for cell membrane and opens up new opportunities for magnetic cell separation and recovery that may be of crucial interest for the development of cellular therapies.
authors.affiliation: Centre for Cell Engineering, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. akgupta25@hotmail.com
authors.forename: Ajay Kumar
authors.initials: AK
authors.lastname: Gupta
authors.forename: Catherine
authors.initials: C
authors.lastname: Berry
authors.forename: Mona
authors.initials: M
authors.lastname: Gupta
authors.forename: Adam
authors.initials: A
authors.lastname: Curtis
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry*; D008024:Ligands; D008422:Materials Testing; D036103:Nanotechnology / Q000379:methods; D043942:Nanotubes / Q000737:chemistry / Q000648:ultrastructure*; D010316:Particle Size; D011956:Receptors, Cell Surface / Q000378:metabolism; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible; D007328:Insulin; D008024:Ligands; D011956:Receptors, Cell Surface