Effects of Serum Adsorption on Cellular Uptake Profile and Consequent Impact of Titanium Dioxide Nanoparticles on Human Lung Cell Lines

Exposure to fetal bovine serum (FBS) is shown herein to reduce the aggregate size of titanium dioxide (TiO₂) nanoparticles, affecting uptake and consequent effect on A549 and H1299 human lung cell lines. Initially, the cellular uptake of the FBS-treated TiO₂ was lower than that of non-FBS-treated TiO₂. Expulsion of particles was then observed, followed by a second phase of uptake of FBS-treated TiO₂, resulting in an increase in the cellular content of FBS-treated TiO₂, eventually exceeding the amount by cells exposed to non-FBS-treated TiO₂. Surface adsorbed vitronectin and the clathrin-mediated endocytosis pathway were shown to regulate the uptake of TiO₂ into A549 cells, while the endocytosis mechanism responsible remains elusive for H1299. Intriguingly, nystatin treatment was shown to have the unexpected effect of increasing nanoparticle uptake into the A549 cells <i>via</i> an alternate endocytic pathway. The surface adsorbed serum components were found to provide some protection from the cytotoxic effect of endocytosed TiO₂ nanoparticles

Controlled Direct Growth of Polymer Shell on Upconversion Nanoparticle Surface via Visible Light Regulated Polymerization

Lanthanide-doped upconversion nanoparticles (UCNPs) have unique photoluminescent properties that are useful in many biomedical applications. Modification of UCNPs with a polymer layer can confer additional functionality such as biocompatibility, stability <i>in vivo</i>, or drug delivery capability. It is also important that the modification process can be controlled precisely and without having adverse effects on the UCNPs luminescence properties. Herein, a polymer shell was grafted directly from the surface of UCNPs (grafting from) via visible light (λ_max = 635 nm, 0.7 mW/cm²) regulated photoenergy/electron transfer–reversible addition fragmentation chain transfer polymerization (PET-RAFT). The polymerization kinetics, grafting density, and thickness of the surface-tethered polymer chains can be tuned precisely by adjusting the monomer and RAFT agent ratio or the light exposure time. This approach also permits temporal control of the polymerization process. That is, the polymerization process can be initiated, halted, or terminated by switching the light source on and off. By limiting the non-radiative decay caused by surface defects, as well as from vibrational deactivation from solvents, the polymer shell enhanced the upconversion luminescence of the silica-coated UCNPs. This investigation paves the way for the development of UCNPs with controlled properties for various application requirements

Insight into Serum Protein Interactions with Functionalized Magnetic Nanoparticles in Biological Media

Surface modification with linear polymethacrylic acid (20 kDa), linear and branched polyethylenimine (25 kDa), and branched oligoethylenimine (800 Da) is commonly used to improve the function of magnetite nanoparticles (MNPs) in many biomedical applications. These polymers were shown herein to have different adsorption capacity and anticipated conformations on the surface of MNPs due to differences in their functional groups, architectures, and molecular weight. This in turn affects the interaction of MNPs surfaces with biological serum proteins (fetal bovine serum). MNPs coated with 25 kDa branched polyethylenimine were found to attract the highest amount of serum protein while MNPs coated with 20 kDa linear polymethacrylic acid adsorbed the least. The type and amount of protein adsorbed, and the surface conformation of the polymer was shown to affect the size stability of the MNPs in a model biological media (RPMI-1640). A moderate reduction in <i>r</i>₂ relaxivity was also observed for MNPs suspended in RPMI-1640 containing serum protein compared to the same particles suspended in water. However, the relaxivities following protein adsorption are still relatively high making the use of these polymer-coated MNPs as Magnetic Resonance Imaging (MRI) contrast agents feasible. This work shows that through judicious selection of functionalization polymers and elucidation of the factors governing the stabilization mechanism, the design of nanoparticles for applications in biologically relevant conditions can be improved