AVS 57th International Symposium & Exhibition
    Biomaterial Interfaces Tuesday Sessions
       Session BI-TuM

Paper BI-TuM11
Rare Earth Nanoparticles - Biocompatibility Studies: Interaction with Human Neutrophil Granulocytes

Tuesday, October 19, 2010, 11:20 am, Room Taos

Session: Cells on Surfaces
Presenter: C. Skoglund, Linköping University, Sweden
Authors: N. Abrikossova, Linköping University, Sweden
C. Skoglund, Linköping University, Sweden
M. Ahren, Linköping University, Sweden
L. Selegård, Linköping University, Sweden
T. Bengtsson, Örebro University, Sweden
K. Uvdal, Linköping University, Sweden
Correspondent: Click to Email

Rare-earth metal nanoparticles are among the most promising candidates to be used as probes for visualization and targeted drug delivery. Compared to the ion-based gadolinium containing complexes used clinically as contrast agents today, gadolinium oxide (Gd2O3) nanoparticles show a considerably improved relaxivity and thus enable an increased resolution and an increased contrast enhancement. However, surface modification of these nanoparticles is essential in order to improve the biocompatibility and diminish any potential toxic effects. In the present study we have evaluated the impact of Gd2O3 nanoparticles (as synthesized, dialyzed, and functionalized with polyethyleneglycol, PEG) on the production of reactive oxygen species (ROS) from human neutrophils.

Gd2O3 nanoparticles were synthesized (via the polyol route), functionalized with PEG and characterized as previously described in Ahren et al.1. Neutrophil granulocytes were isolated from heparinized whole blood using density gradient centrifugation. Generation of ROS by neutrophils upon addition of IgG-opsonized yeast, in presence and/or absence of as synthesized, dialyzed and functionalized Gd2O3 nanoparticles was studied with luminol-dependent chemiluminescence. In addition, the morphology of neutrophils after interaction with Gd2O3 nanoparticles was evaluated by fluorescence microscopy.

The ROS production from neutrophils challenged with IgG-opsonized yeast after exposure to as synthesized Gd2O3 nanoparticles was significantly decreased compared to control without nanoparticles. This indicates that the as synthesized nanoparticles are not well suited to be directly used in a living system without further modification. However, after dialysis and functionalization with PEG, no inhibitory effects were observed, possibly indicating that the high concentration of diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects. Indeed, we in the present study also show that even a low concentration of DEG (0.3%) inhibits neutrophil ROS production. Our results indicate that dialyzed and PEG-functionalized Gd2O3 particles may be suitable in an in vivo situation as they do not impair the neutrophils capacity to produce ROS in response to a pray.

1 Ahren M, Selegård L, Klasson A, Söderlund F, Abrikossova N, Skoglund C, Bengtsson T, Engström M, Käll P.O, and Uvdal K, Synthesis and characterization of PEGylated Gd2O3 nanoparticles for MRI contrast enhancement. Langmuir 2010, 26 (8) 5753-5762