miR-29b and retinoic acid co-delivery: a promising tool to induce a synergistic antitumoral effect in non-small cell lun
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ORIGINAL ARTICLE
miR-29b and retinoic acid co-delivery: a promising tool to induce a synergistic antitumoral effect in non-small cell lung cancer cells Mariana Magalhães 1,2 & Joana Jorge 3,4 & Ana Cristina Gonçalves 3,4 & Ana Bela Sarmento-Ribeiro 3,4,5 & Rui Carvalho 2,6 & Ana Figueiras 1,2 & Ana Cláudia Santos 1,2 & Francisco Veiga 1,2
# Controlled Release Society 2020
Abstract 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 codelivery 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.
Keywords miR-29b . Retinoic acid . Micelleplexes . RNAi-based therapy . Non-small cell lung cancer Abbreviations NSCLC non-small cell lung cancer SCLC small cell lung cancer RA retinoic acid sRNA small RNA RNAi RNA interference miRNA microRNA mRNA messenger RNA
3’-UTR DNMT CpGi FBS NC AV PI PEI
3′-untranslated region DNA methyltransferases CpG islands fetal bovine serum scrambled sequence annexin V propidium iodide polyethyleneimine
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13346-020-00768-7) contains supplementary material, which is available to authorized users. * Mariana Magalhães [email protected] * Francisco Veiga [email protected] 1
2
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
3
Laboratory of Oncobiology and Hematology, University Clinic of Hematology and Applied Molecular Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
4
Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
5
Clinical Hematology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), C
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