Reversible control of protein corona formation on gold nanoparticles using host-guest interactions

When nanoparticles (NPs) are exposed to biological media, proteins are adsorbed, forming a so-called protein corona (PC). This cloud of protein aggregates hampers the targeting and transport capabilities of the NPs, thereby compromising their biomedical applications. Therefore, there is a high interest in the development of technologies that allow control over PC formation, as this would provide a handle to manipulate NPs in biological fluids. We present a strategy that enables the reversible disruption of the PC using external stimuli, thereby allowing a precise regulation of NP cellular uptake. The approach, demonstrated for gold nanoparticles (AuNPs), is based on a biorthogonal, supramolecular host-guest interactions between an anionic dye bound to the AuNP surface and a positively charged macromolecular cage. This supramolecular complex effectively behaves as a zwitterionic NP ligand, which is able not only to prevent PC formation but also to disrupt a previously formed hard corona. With this supramolecular stimulus, the cellular internalization of AuNPs can be enhanced by up to 30-fold in some cases, and even NP cellular uptake in phagocytic cells can be regulated. Additionally, we demonstrate that the conditional cell uptake of purposely designed gold nanorods can be used to selectively enhance photothermal cell death

Synergistic immunomodulatory effect in macrophages mediated by magnetic nanoparticles modified with miRNAs

In this work, we describe the synthesis of magnetic nanoparticles composed of a maghemite core (MNP) and three different coatings (dextran, D-MNP; carboxymethyldextran, CMD-MNP; and dimercaptosuccinic acid, DMSA-MNP). Their interactions with red blood cells, plasma proteins, and macrophages were also assessed. CMD-MNP was selected for its good biosafety profile and for promoting a pro-inflammatory response in macrophages, which was associated with the nature of the coating. Thus, we proposed a smart miRNA delivery system using CMD-MNP as a carrier for cancer immunotherapy applications. Particularly, we prove that CMD-MNP-miRNA155 and CMD-MNP-miRNA125b nanoparticles can display a pro-inflammatory response in human macrophages by increasing the expression of CD80 and the levels of TNF-alpha and IL-6. Hence, our proposed miRNA-delivery nanosystem can be exploited as a new immunotherapeutic tool based on magnetic nanoparticles.Peer reviewe