Tissue and cellular localization of nanoparticles using 35S labeling and light microscopic autoradiography – NanomedSpain

Tissue and cellular localization of nanoparticles using 35S labeling and light microscopic autoradiography

Abstract: Microscopical visualization of nanoparticles in tissues is essential for assessing their distribution in whole organisms and their interaction with the cellular microenvironment, including possible toxic effects. However, labeling of nanoparticles with fluorescent dyes may affect their physicochemical properties. Moreover, the detection… Abstract: Microscopical visualization of nanoparticles in tissues is essential for assessing their distribution in whole organisms and their interaction with the cellular microenvironment, including possible toxic effects. However, labeling of nanoparticles with fluorescent dyes may affect their physicochemical properties. Moreover, the detection of organic nanoparticles in their tissue context often poses a particular challenge due to their closer similarities with biomolecules. As part of a biodistribution and toxicity study on organic anti-inflammatory nanoscaled dendritic polyglycerol sulfate amine (dPGS amine) we have established light microscopic autoradiography (LMA) for the tracking of 35S labeled dPGS in standard histopathological tissue samples following intravenous injection in mice. The dPG35S amine was specifically localized in hepatic Kupffer cells with no histopathologic evidence of toxic, degenerate or inflammatory side effects. The combination of radiolabeling of organic nanoparticles with LMA offers a novel approach for their localization in microscopical slides, also allowing for a simultaneous standard toxicopathology analysis.From the Clinical Editor: In this study, a novel light microscopic autoradiography utilizing 35S isotope demonstrates a combined approach to visualize nanoparticle locations in microscopic slides with no obvious toxicity to the studied cells and with minimal external hazard.Graphical Abstract: Visualization of organic nanoparticles in cells and tissues, with their characteristics close to biomolecules, is particularly challenging. Formerly organic nanoparticles have been localized microscopically after the addition of fluorescent tags. However, the attachment of fluorochrome-molecules to these nanoscaled macromolecules may inevitably change physicochemical properties and subsequently alter their biological behavior in tissues. Here, we introduce a novel strategy for the localization of untagged organic dendritic polygycerol sulfate nanoparticles in mouse tissue. Based on radiolabeling the light microscopic autoradiography circumvents the drawbacks of fluorescent tagging and allows for a simultaneous light microscopical histopathology examination of the tissues for routine toxicology testing.

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