Protein Assembly on Iron Oxide Nanoparticles for Enhanced In Vivo Delivery in HeLa Cells

Nanoparticles (NPs) have great potential as therapeutic drug carriers and for diagnostic purposes. The efficacy depends on the ability to control cellular uptake and destination in vivo. A route to achieve this goal is the functionalization of NP surfaces with proteins that have specific interactions with cell receptors. However, the specific binding affinity is often lost when the NPs are placed in biological (in-vivo) media while there has been success maintaining protein-receptor interactions in simple solutions in vitro. Here we demonstrate that the specific interaction between transferrin-coated maghemite NPs and the transferrin receptor 1 is retained in the presence of fetal calf serum, especially for particles in the size range of 10 to 100 nm. Coarse-grained simulations of protein binding to NP surfaces suggest that the size of the functionalized NPs influences the orientation and possibly the activity of the transferrin molecules used for functionalization. The results illustrate that functionalized NPs hold potential as therapeutics when their properties are properly controlled and develop a supporting hypothesis at the molecular/protein-scale level.