Abstract
Medical imaging is an active field of research that fosters the necessity for novel multimodal imaging probes. In this line, nanoparticle-based contrast agents are of special interest, since those can host functional entities either within their interior, reducing potential toxic effects of the imaging tracers, or on their surface, providing high payloads of probes, due to their large surface-to-volume ratio. The long-term stability of the particles in solution is an aspect usually under-tackled during probe design in research laboratories, since their performance is generally tested briefly after synthesis. This may jeopardize a later translation into practical medical devices, due to stability reasons. To dig into the effects of nanoparticle aging in solution, with respect to their behavior in vivo, iron oxide stealth nanoparticles were used at two stages (3 weeks vs. 9 months in solution), analyzing their biodistribution in mice. Both sets of nanoprobes showed similar sizes, zeta potentials, and morphology, as observed by dynamic light scattering (DLS) and transmission electronic microscopy (TEM), but fresh nanoparticles accumulated in the kidneys after systemic administration, while aged ones accumulated in liver and spleen, confirming an enormous effect of particle aging on their in vivo behavior, despite barely noticeable changes perceived on a simple inspection of their structural integrity.
Highlights
Medical imaging is seeking to overcome inherent limitations regarding sensitivity, specificity, resolution, and scanning time, by means of acquisition of multimodal images
We describe the effect of aging of those nanoprobes in solution, relating the physicochemical modifications suffered by the particle with the changes in their in vivo biodistribution in mice, as determined by MagneticResonance Imaging (MRI)
iron oxide nanoparticle (IONP) were characterized by transmission electron microscopy after different times in solution, following synthesis
Summary
Medical imaging is seeking to overcome inherent limitations regarding sensitivity, specificity, resolution, and scanning time, by means of acquisition of multimodal images This has motivated the development of novel scanners able to combine several imaging techniques (e.g., positron emission tomography and magnetic resonance imaging PET/MRI scanners), and the growth of a research field. Because of its inherent relatively low sensitivity, in comparison with other imaging techniques (e.g., nuclear imaging), and to speed up acquisition times, an important research activity exists around MRI, aiming at producing MRI contrast agents. Those agents usually combine their magnetic properties with other physical properties (e.g., fluorescence or radioactive decay) for multimodal imaging purposes [1,2,3,4]. The use of iron oxide nanoparticles (IONPs) as MRI contrast agents started 20 years ago, becoming very popular due to their ability to dramatically reduce T2 relaxation times in organs such as liver, spleen, and bone marrow, by selective uptake and accumulation in cells belonging to the mononuclear phagocyte or reticuloendothelial system (RES)
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