(783f) In Vivo Assessment of Temporal and Spatial Behavior of Carboxyl Methyl Dextran Iron Oxide Nanoparticles in Breast Cancer Model

Hyperthermia consists of heating an organ or tissue to temperatures between 41 to 46˚C, which induces damage to cancer cells and triggers cell death and/or cell protective mechanisms. Magnetic fluid hyperthermia is being proposed to deliver heat at the desired area using magnetic nanoparticles. The main challenge in this area is to reach the necessary nanoparticle concentration in the tumor in order to be able to reach the necessary temperatures when administered through tail vein injection, to achieve this goal the temporal and spatial properties of the particles need to be assessed.    For this purpose, iron oxide nanoparticles functionalized with carboxyl methyl dextran with various degrees of negative charge have been developed. Particles were designed to have different amounts of carboxyl groups per chain (30, 23 and 5 COOH). The objective of this work is to assess the in vivo temporal and spatial behavior of the particles described herein to assess the effect of particle charge on tumor accumulation given that previous work from in vitro uptake experiments with the MCF-7 cell line showed that higher uptake was obtained when higher degrees of negative charge were applied.  For this purpose, in vivo pharmacokinetics and biodistribution experiments were conducted. Pharmacokinetic experiments were performed by injecting nanoparticles to cannulated Wistar rats. Each animal was administered a dose of 58mg Fe/kg. Iron concentration in plasma was measured throughout a 24 hour period at various time intervals.  Results demonstrated that nanoparticle half life was significantly affected and was inversely proportional to nanoparticle charge (higher charge, lower half life).  Values ranged from 16 min for those nanoparticles with higher amounts of carboxyl groups to 4 hours for the 5COOH nanoparticles.  Biodistribution experiments were conducted in Nu/Nu mice inoculated subcutaneously in the torso with MCF-7 cells and after 6 weeks experiments were performed. Particles were injected through tail vein injection at 29 mg Fe/kg of nanoparticles per mice. Mice were dissected after 6 hours and iron concentration was determined in liver, spleen, kidney and tumor using a spectrophotometric technique. Higher particle uptake in the tumor was observed for those particles with the lowest charge.  These results indicate that in vivo temporal and spatial behavior can be significantly affected by surface properties, therefore nanoparticles must be optimized for these purposes.