Title: New Surface Radiolabeling Schemes of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) for Biodistribution Studies

Abstract

Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and 10 easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90 110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate 15 functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with ¹⁴C, with a final activity of 0.097 nCi/mg^-1 of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeledmore » proxies are chemically similar but not chemically identical to the non-20 radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and 25 detection techniques. The radiolabeling approach described here is applicable to the synthesis of a large class of nanomaterials with multiple core and surface functionalities. This work combined with the biodistribution data suggests that the radiolabeling schemes carried out in this study have broad implications for use in pharmacokinetic studies for a variety of nanomaterials.« less

Authors:

Nallathamby, Prakash D. ^[1]; Mortensen, Ninell P. ^[2]; Palko, Heather A. ^[3]; Malfatti, Mike ^[4]; Smith, Catherine ^[5]; Sonnett, Jim ^[5]; Doktycz, Mitchel John ^[2]; Gu, Baohua ^[2]; Roeder, Ryan ^[6]; Wang, Wei ^[2]; Retterer, Scott T. ^[2]

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+ Show Author Affiliations

1. Batelle Memorial Inst., Columbus, OH (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Notre Dame, IN (United States)
2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
3. Battelle Memorial Inst., Columbus, OH (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
4. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
5. Battelle Memorial Inst., Columbus, OH (United States)
6. Univ. of Notre Dame, IN (United States)

Publication Date:

Mon Mar 02 00:00:00 EST 2015

Research Org.:

Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS); Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Org.:

USDOE National Nuclear Security Administration (NNSA)

OSTI Identifier:

1237616

Alternate Identifier(s):

OSTI ID: 1840105

Report Number(s):

LLNL-JRNL-820399
Journal ID: ISSN 2040-3364; 453065013

Grant/Contract Number:  

AC05-00OR22725; AC52-07NA27344

Resource Type:

Accepted Manuscript

Journal Name:

Nanoscale

Additional Journal Information:

Journal Volume: 7; Journal Issue: 15; Journal ID: ISSN 2040-3364

Publisher:

Royal Society of Chemistry

Country of Publication:

United States

Language:

English

Subject:

77 NANOSCIENCE AND NANOTECHNOLOGY