Iterative nanoparticle bioengineering enabled by x-ray fluorescence imaging

Abstract

Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.

Toxicity and magnetometry evaluation of the uptake of core-shell maghemite-silica nanoparticles by neuroblastoma cells

“…In addition, although the MTT method has been widely used to measure cell toxicity in cell cultures, through the variation of cell metabolic activity, in our case, the nature of our MNPs makes this method not viable, as they alter the spectrophotometric measurement especially in the µg ml −1 range (data not shown), as already described for other MNPs [53]. Real-time cell analysis, founded on impedance-based measurements, offers a compelling solution to circumvent interference concerns associated with nanoparticles, including those with silica coatings and fluorescence, and would be an accurate method to evaluate nanoparticle cytotoxicity in the future [54][55][56][57].…”