Quantitative Comparison of Tumor Delivery for Multiple Targeted Nanoparticles Simultaneously by Multiplex ICP-MS

Abstract

Given the rapidly expanding library of disease biomarkers and targeting agents, the number of unique targeted nanoparticles is growing exponentially. The high variability and expense of animal testing often makes it unfeasible to examine this large number of nanoparticles in vivo. This often leads to the investigation of a single formulation that performed best in vitro. However, nanoparticle performance in vivo depends on many variables, many of which cannot be adequately assessed with cell-based assays. To address this issue, we developed a lanthanide-doped nanoparticle method that allows quantitative comparison of multiple targeted nanoparticles simultaneously. Specifically, superparamagnetic iron oxide (SPIO) nanoparticles with different targeting ligands were created, each with a unique lanthanide dopant. Following the simultaneous injection of the various SPIO compositions into tumor-bearing mice, inductively coupled plasma mass spectroscopy was used to quantitatively and orthogonally assess the concentration of each SPIO composition in serial blood and resected tumor samples.

Evaluation of Toxicity and Neural Uptake In Vitro and In Vivo of Superparamagnetic Iron Oxide Nanoparticles

“…Publications about in vivo SPIO application indicate that the concentrations applied in our in vitro experiments are approximately in the range used for in vivo treatments. Elias et al [ 27 ] injected 3.75 mg Fe/kg intravenously in rodents. Assuming that blood volume is approximately 7% of body weight [ 28 ], this translates to 50–55 µg Fe/mL blood volume.…”

LA-ICP-MS Allows Quantitative Microscopy of Europium-Doped Iron Oxide Nanoparticles and is a Possible Alternative to Ambiguous Prussian Blue Iron Staining

“…Additionally, the technique could be combined with ICP-MS for biodistribution studies. 34 Furthermore, doping of different nanoparticles with different elements (e.g., different lanthanides owing to the good detectability) would allow their differentiation after simultaneous administration (multiplexing) at the histological level, for instance, to investigate the effects of different surface coatings. Finally, the technique is likely applicable to other nanoparticles, for instance by incorporation of lanthanides using heat-induced labeling.…”

Atomic spectrometry update: review of advances in atomic spectrometry and related techniques

“…The method was used to determine glycoproteins in real human serum with recoveries of over 97%. 35,36 1.1.2 Nebulisation. By taking advantage of the amplifying effect of the Au-NP the LOD was 86 cells, which is comparable with electrochemical detection but faster.…”