Replication of “Nano-Flares: Probes for Transfection and mRNA Detection in Living Cells”

In hundreds of articles published over the past two decades, nanoparticles have been described as probes for sensing and imaging of a variety of intracellular cytosolic targets. However, nanoparticles generally enter cells by endocytosis with only a small fraction reaching the cytosol. Most of those articles do not describe the mechanisms of nanoparticles entry into the cell and therefore the paradox of sensing a target in the cytosol when most particles do not access that compartment remains. To address this paradox, we are initiating a replication project of some of the most influential articles in this field with the aim of confirming their ability to detect their targets and getting additional insights into their intracellular localisation. This article is a pre-registered report for the second replication of this project, namely the replication of Seferos et al ‘Nano-Flares: Probes for Transfection and mRNA Detection in Living Cells’. To achieve our aim, we will carry out both a direct replication of the experiments in the original article, with the addition of some experiments and controls (in particular optical and electron microscopy). We hope that this study will contribute to a better understanding of the intracellular fate of nanoparticles and, with the help of the scientific community, help set standards in the design and reporting of studies in this field.