Nanomedicine emerged some decades ago with the hope to be the solution for most unmet medical needs. However, tracking materials at nanoscale is challenging to their reduced size, below the resolution limit of most conventional techniques. In this context, we propose the use of direct stochastic optical reconstruction microscopy (dSTORM) to study time stability and cell trafficking after transfection of oligopeptide end-modified poly(β-aminoester) (OM-pBAE) nanoparticles. We selected different combinations of cationic end oligopeptides (arginine -R; histidine -H; and lysine -K) among polymer libraries, since the oligopeptide combination demonstrated to be useful for different applications, such as vaccination and gene silencing. We demonstrate that their time evolution as well as their cell uptake and trafficking are dependent on the oligopeptide. This study opens the pave to broad mechanistic studies at nanoscale that could enable a rational selection of specific pBAE nanoparticles composition after determining their stability and cell trafficking.
The Front Cover shows the trafficking of polyplexes inside cells to deliver oligonucleotides. Many steps are needed from internalization, endosomal escape, and decomplexation for a successful delivery, but they are too small to be visualized using classical fluorescence microscopy. Alternatively, the localization and composition of these nanomaterials can be studied using quantitative super‐resolution microscopy as shown in the STORM image of polyplexes in this cover. Created with Biorender.com by Roger Riera. More information can be found in the Full Paper by Roger Riera, Cristina Fornaguera, Lorenzo Albertazzi et al.
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