Prolonging the circulatory retention of SPIONs using dextran sulfate: in vivo tracking achieved by functionalisation with near-infrared dyes

Abstract

The rapid reticuloendothelial system (RES) mediated clearance of superparamagnetic iron oxide nanoparticles (SPIONs) from circulation is considered a major limitation of their clinical utility. We aimed to address this by using dextran sulfate 500 (DSO4 500), a Kupffer cell blocking agent, to prolong SPIONs circulatory time. Blood concentrations of SPIONs are difficult to quantify due to the presence of haemoglobin. We therefore developed methods to functionalise SPIONs with near-infrared (NIR) dyes in order to trace their biodistribution. Two SPIONs were investigated: Nanomag®-D-spio-NH(2) and Ferucarbotran. Nanomag®-D-spio-NH(2) was functionalised using NHS (N-hydroxysuccinimide) ester NIR dye and Ferucarbotran was labelled using periodate oxidation followed by reductive amination or a combination of EDC (ethyl(dimethylaminopropyl) carbodiimide )/NHS and click chemistries. Stability after conjugation was confirmed by dynamic light scattering (DLS), superconducting quantum interference device (SQUID) and transmission electron microscopy (TEM). In vivo experiments with the functionalised SPIONs showed a significant improvement in SPIONs blood concentrations in mice pre-treated with dextran sulfate sodium salt 500 (DSO4 500).

Tracking short-term biodistribution and long-term clearance of SPIO tracers in magnetic particle imaging

“…Ferucarbotran is an aqueous suspension of multi-core carboxydextran-coated magnetite nanoparticles, originally designed as a liver-targeting MRI contrast agent (Abdollah et al 2014), and adopted for use in MPI (Lüdtke-Buzug et al 2009; Ferguson et al 2013). LS-008 is a PEG-coated single-core magnetite nanoparticle, designed as a long circulating MPI tracer (Ferguson et al 2015; Kemp et al 2016; Ferguson et al 2013).…”

Use of aminated hulls of sunflower seeds for the removal of anionic dyes from aqueous solutions

“…Amination of polysaccharides is often preceded by polysaccharide activation with epichlorohydrin which enriches the material in epoxide groups that easily attach amines via addition (Liu et al 2013;Razavi and Akhlaghinia 2015;Abdollah et al 2014).…”

Antibody-Targeted Nanoparticles for Cancer Treatment

“…Whilst this characteristic lends itself well to SPION use as contrast agents, it is detrimental to achieving sufficient intratumoural SPION concentrations to generate therapeutic heating. A number of solutions have been proposed to overcome this, including the use of blocking agents to prolong SPION circulatory time [128], tailoring the NP surface chemistries or the targeting moieties to optimise cellular interactions of SPIONs [41,129] or direct intratumoural injection with targeting antibodies functioning to retain SPIONs at the injection site.…”