The In-Vivo Use of Superparamagnetic XXXX Nanoparticles to Detect Inflammation Elicits a Cytokine Response but Does Not Aggravate Experimental @entity625 .

@entity32 @entity558 @entity939 @entity4832 @entity625 @entity19 @entity1933 @entity1990 @entity68
BACKGROUND: Superparamagnetic @entity1933 Nanoparticles (SPION) are used in diagnostic imaging of a variety of different diseases. For such in-vivo application, an additional coating with a polymer, for example @entity4832 ( @entity939 ), is needed to stabilize the SPION and prevent aggregation. As the particles are foreign to the body, reaction against the SPION could occur. In this study we investigated the effects that SPION may have on experimental @entity625 after intra-articular (i.a.) or intravenous (i.v.) injection. METHODS: @entity939 -coated SPION were injected either i.a. (6 or 24  g @entity68 ) or i.v. (100  g or 1 mg @entity68 ) into na  ve @entity1990 deficient ( @entity1990 -/-) or wild-type C57Bl/6 @entity19 , or C57Bl/6 mice with antigen-induced @entity625 . As control, some @entity19 were injected with @entity939 or PBS. MR imaging was performed at 1 and 7 days after injection. @entity19 were sacrificed 2 hours and 1, 2, 7, 10 and 14 days after injection of the SPION, and RNA from synovium and liver was isolated for pro-inflammatory gene expression analysis. Serum cytokine measurements and whole knee joint histology were also performed. RESULTS: Injection of a high dose of SPION or @entity939 into na  ve knee joints resulted in an immediate upregulation of pro-inflammatory gene expression in the synovium. A similar gene expression profile was observed after SPION or @entity939 injection into knee joints of @entity1990 -/- @entity19 , indicating that this effect is not due to @entity558 contamination. Histological analysis of the knee joints also revealed @entity32 after SPION injection. Two hours after i.v. injection of SPION or @entity939 into na  ve @entity19 , an upregulation of pro-inflammatory gene expression was detected in the liver. Administration of SPION or @entity939 into arthritic @entity19 via i.a. injection did not result in an upregulation in gene expression and also no additional effects were observed on histology. MR imaging and histology showed long-term retention of SPION in the inflamed joint. However, 14 days after the injections no long-term effects were evident for gene expression, histology or serum cytokine concentrations. CONCLUSIONS: Injection of SPION, either locally or systemically, gives an acute inflammatory response. In the long term, up to 14 days after the injection, while the SPION reside in the joint, no further activating effects of SPION were observed. Hence, we conclude that SPION do not aggravate @entity625 and can therefore be used safely to detect joint @entity32 by MR imaging.
