Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 9, Issue 2, Pages 194-201Publisher
ELSEVIER
DOI: 10.1016/j.nano.2012.05.015
Keywords
Ligand density; SPIO; Targeting; Click chemistry; Nanoparticle
Funding
- National Institute of Health (NIBIB) [R01-EB012065, R21-EB013226]
- National Institute of Health (NCI) [R01-CA157766]
- National Institute of Health (NHLBI) [R01-HL087036]
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It is generally accepted that the presentation of multiple ligands on a nanoparticle (NP) surface can improve cell targeting; however, little work has been done to determine whether an optimal ligand density exists. We have recently developed a site-specific bioconjugation strategy that allows for distinct control of ligand density on a NP through the combined utilization of expressed protein ligation (EPL) and copper-free click chemistry. This EPL-Click conjugation strategy was applied to create superparamagnetic iron oxide (SPIO) NPs labeled with HER2/neu targeting affibodies at differing ligand densities. It was discovered that an intermediate ligand density provided statistically significant improvements in cell binding in comparison with higher and lower ligand densities. This intermediate optimal ligand density was conserved across NPs with differing hydrodynamic diameters, different HER2/neu targeting ligands and also to cells with lower receptor densities. Additionally, an intermediate optimal ligand density was also evident when NPs were labeled with folic acid.
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