Dual Mode Iron Oxide Nanoparticles for Bio-Distribution Studies in Life Sciences

Dual Mode Iron Oxide Nanoparticles for  Bio-Distribution Studies in Life Sciences

Prakash D. Nallathamby^1,2, Heather A. Palko^1,3, Wei Wang², Mike Malfatti³ and Scott T. Retterer²

¹Battelle Center for Fundamental and Applied Systems Toxicology, Battelle Memorial Institute, Columbus-OH; ²BESD, Oak Ridge National Lab, Oak Ridge-TN 37831, ³Biosciences and Biotechnology Division, Physical and Life Sciences, Lawrence Livermore National Lab Livermore, CA 94550

Assessing bio-distribution and pharmacokinetic (PK) properties are key steps in designing drug delivery vehicles. With this in mind, we have synthesized water soluble, ¹⁴C (t_1/2=5730 years) labeled, magnetic iron oxide nanoparticles (~10nm) with differing surface functional groups (carboxylic acid or amine) to assess how surface properties affect bio-distribution in vivo.  The radiolabeling reaction schemes were highly flexible and the degree of radiolabeling was controllably varied from 0.1² nCi/mg to 0.1 mCi/mg without any increase in reaction times.  The reaction schemes involved converting silano-organic moieties on the nanoparticle, to carboxylic acid (-COOH) functional groups using substitution chemistry or to amine (-NH₃) functional groups using polymer chemistry. The bio-distribution and PK properties were determined using Accelerator Mass Spectroscopy (AMS), an ultrasensitive (10^-18 moles) spectrometric technique that allows quantitation of ¹⁴C in small amounts of sample.  The radio-labeling approach used in these studies was significant as the radio-labeled probes had the same chemical properties as the non-labeled probes they were meant to mimic, which provides for a comparable set of data.  Furthermore, the use of a magnetic core as the nano-carrier for the radiolabels allows for dual detection schemes, which will increase the accuracy of the bio-distribution data. The synthesized particles in this work have implications for use in many biological applications aside from drug delivery