miR-29b and retinoic acid co-delivery: a promising tool to induce a synergistic antitumoral effect in non-small cell lung cancer cells.

: The high incidence, late diagnosis, and aggressive profile of lung cancer limit the treatment options, causing a reduced survival rate. Consequently, RNAi-based therapy appears as a potential approach to treat non-small cell lung cancer (NSCLC). This approach is based on the delivery of small RNAs, involved in the regulation of key cell pathways, to treat complex diseases among others. Concerning that, the aim of this work was focused on the co-delivery of miR-29b and retinoic acid (RA) into NSCLC cells by multifunctional micellar nanosystems (Pluronic® P123 or Pluronic® P103 linked to polyethyleneimine (PEI)). The developed P103-PEI-RA/miR-29b (10/1) presented better results and most attractive properties, promoting efficient delivery of miR-29b, as well as revealing a significant antitumoral activity promoted by a synergistic effect between miR-29b expression and RA deliver. Furthermore, the developed therapeutic approach was able to significantly decrease cell viability and migration, as well as induce cell cycle arrest and epigenetic regulation in NSCLC cells. Thus, this work outcome enables to discover a hopeful system to deliver therapeutic miRNAs, crafting a novel RNAi-based therapy combined with RA to treat NSCLC. Graphical abstract.