miR-21/Gemini surfactant-capped gold nanoparticles as potential therapeutic complexes: Synthesis, characterization and in vivo nanotoxicity probes

摘要

MicroRNAs (miRNAs) provide a unique mechanism of gene regulation and play a key role in different pathologies ranging from metabolic diseases to cancer. Thus, they are attractive candidates as therapeutic targets in the clinic. However, delivering miRNAs to specific tissues remains challenging, due to their inherent instability and their low diffusion into tissues, as well as a lack of effective means of delivering them to the cytosols of the specific cells. To overcome these challenges, we constructed a delivery vehicle based on novel gold nanosystems having gemini surfactants which offer a high capacity to induce the miRNAs compression, high stability and cell-entry capability. The synthesis of gold nanoparticles with a positive surface charge, Au@16-Ph-16/miR-21 and Au@16-3-16/miR-21, was carried out in a three-step process. In this method, the hydrogen tetrachloroaurate, sodium tetrahydroborate and 16-Ph-16 or 16-3-16 compounds were used as gold precursor, reducing agent and stabilizers, respectively. The nanoparticles obtained were then covered with miR-21 polymer and were characterized by UV-visible spectroscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering and zeta potential to measure size and charge distribution. Finally, toxicity was assessed in vivo in mice. Moreover, coherent anti-Stokes Raman spectroscopy and histochemistry analyses showed that Au@16-Ph-16/miR-21 and Au@16-3-16/miR-21 exhibited no toxicity, antimicrobial and biocompatible activities. These nanosystems can be a valuable alternative in therapies associated with diseases where miRNAs play a regulatory role that may be decisive in the improvement or cure of patients. All these characteristics could make of these nano-systems the best potential therapeutic molecules. (C) 2020 Elsevier B.V. All rights reserved.