In vitro biophysical and biological characterization of lipid nanoparticles Co-encapsulating oncosuppressors miR-199b-5p and miR-204-5p as potentiators of target therapy in metastatic melanoma

Luigi Fattore, Virginia Campani, Ciro Francesco Ruggiero, Valentina Salvati, Domenico Liguoro, Lorena Scotti, Gerardo Botti, Paolo Antonio Ascierto, Rita Mancini, Giuseppe De Rosa, Gennaro Ciliberto

Research output: Contribution to journalArticle

Abstract

Uncontrolled MAPK signaling is the main oncogenic driver in metastatic melanomas bearing mutations in BRAF kinase. These tumors are currently treated with the combination of BRAF/MEK inhibitors (MAPKi), but this therapy is plagued by drug resistance. In this context we recently discovered that several microRNAs are involved in the development of drug resistance. In particular miR-204-5p and miR-199b-5p were found to function as antagonists of resistance because their enforced overexpression is able to inhibit melanoma cell growth in vitro either alone or in combination with MAPKi. However, the use of miRNAs in therapy is hampered by their rapid degradation in serum and biological fluids, as well as by the poor intracellular uptake. Here, we developed lipid nanoparticles (LNPs) encapsulating miR-204-5p, miR-199b-5p individually or in combination. We obtained LNPs with mean diameters < 200 nm and high miRNA encapsulation efficiency. These formulations were tested in vitro on several melanoma cell lines sensitive to MAPKi or rendered drug resistant. Our results show that LNPs encapsulating combinations of the two oncosuppressor miRNAs are highly efficient in impairing melanoma cell proliferation and viability, affect key signaling pathways involved in melanoma cell survival, and potentiate the efficacy of drugs inhibiting BRAF and MEK. These results warrant further assessment of the anti-tumor efficacy of oncosuppressor miRNAs encapsulating LNPs in in vivo tumor models.

Original languageEnglish
Article number1930
JournalInternational Journal of Molecular Sciences
Volume21
Issue number6
DOIs
Publication statusPublished - Mar 2 2020

Keywords

  • Drug resistance
  • Melanoma
  • MiRNAs
  • Nanoparticles
  • Therapeutics

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'In vitro biophysical and biological characterization of lipid nanoparticles Co-encapsulating oncosuppressors miR-199b-5p and miR-204-5p as potentiators of target therapy in metastatic melanoma'. Together they form a unique fingerprint.

  • Cite this