Cationic Lipid Nanoparticles for miR-34A Delivery to Lung Cancer Cells: Comparative Evaluation of Plasmid DNA and
Mustafa Kotmakci1, Zekeriya Duzgun2,3, Ugur Karagoz1,4
1Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Campus-Bornova, Izmir, 35040, Türkiye.
Introduction:
MicroRNAs (miRNAs) are promising diagnostic biomarkers and therapeutic agents with therapeutic applications based on either miRNA mimics or antagonists. The objective of this study was to develop a cationic lipid nanoparticle (cLNP) system for the targeted delivery of miRNAs to cancer cells. We focused on the tumor-suppressor miR-34a, which is downregulated in many cancers, yet its clinical use remains limited by the lack of an efficient and safe delivery system.
Methods:
LNPs were prepared with solid lipids using the hot microemulsion method. Both plasmid DNA (P-miR34a) and oligonucleotide (O-miR34a) forms of miR-34a were complexed with cLNPs and characterized in terms of complex formation ability, particle size, and morphology. Cell proliferation and miR-34a expression levels were assessed after cLNP-miR-34a complexes were applied to normal and cancer cells.
Results:
The miRNA-loaded complexes had a particle size of about 66 nm and a zeta potential value of +17.6 mV, while pDNA-loaded complexes had a particle size of approx. 114 nm and a zeta potential value of +3.9 mV. cLNPs showed dose-dependent cytotoxicity on normal and malignant cell lines. O-miR34a complexes significantly increased miR-34a levels in Calu1, HCC827 and H1299 cells, whereas P-miR34a complexes significantly enhanced expression in Calu1 and H1299 cells but not in HCC827.
Discussion:
Our results showed that cLNP complexes, carrying the oligonucleotide form, successfully delivered miR-34a to all cell lines.
Conclusion:
Future studies should evaluate these formulations in in vivo models in order to evaluate their targeting specificity and therapeutic efficacy.
