Delivery of miRNA-126 through folic acid-targeted biocompatible polymeric nanoparticles for effective lung cancer therapy

Abstract

Objective: Nanoparticle-based drug delivery systems (DDSs) have been playing a considerable role in the eradication of cancer. In this experimental study, we designed and synthesized folic acid (FA)-decorated chitosan (CS) nanocarrier for targeted delivery of miR-126 (as a therapeutic agent) to lung cancer A549 cells. Materials and methods: Therefore, the FA-CS-miR-126 nano-complex was perfectly developed and characterized by various analytical devices such as Fourier transform infrared (FT-IR) and dynamic light scattering (DLS) spectroscopies and as well as transmission electron microscopy (TEM). The size was determined lower than 100 nm for synthetics. Then, a gel retardation assay was performed to investigate the entrapment efficiency of nano-complex. Afterward, the sort of in vitro assays was implemented on A549 (FA receptor-positive lung cancer cell line) and MRC5 (normal human diploid cell line) to evaluate the therapeutic efficiency of FA-CS-miR-126. Results: As the cell viability (40.7 ± 2.98% cell viability after 72 h treatment with 500 nM), migration assay (weaker migration after 24 h and 48 h), apoptotic and autophagy genes expression level (Caspse9: sixfolds; BAX: 17 folds; ATG5: fourfolds; and BECLIN1: threefolds more than the control group), the reduced expression level of EGF-L7, as a target gene for miR-126 was evaluated by Real-Time PCR too, then, cell cycle arrest (8.66% of cells in sub-G1 phase), and cell apoptosis assay (21.0% of cancer cell in late apoptosis phase) were scrutinized. Conclusion: These results are remarkably approved the biocompatible and efficient performance of FA-CS-miR-126 as a promising DDS.

Regulation and therapeutic potentials of microRNAs to non-small cell lung cancer

“…Polyethyleneimine (PEI), the most common type of polyplexes, was used to deliver miR-33a and miR-145 to colon carcinoma tissues in a mouse model, resulting in tumor proliferation reduction and cell apoptosis increase [ 270 ]. Another study used a three-layered polyplex of a PEI core, a polyethylene glycol (PEG) intermediate layer, and a folic acid-modified chitosan outer layer to systemically deliver miRNA-126 into lung cancer cells [ 271 ]. The results showed that this polyplex could efficiently deliver miRNA-126 and inhibit tumor growth in vivo [ 271 ].…”

“…Another study used a three-layered polyplex of a PEI core, a polyethylene glycol (PEG) intermediate layer, and a folic acid-modified chitosan outer layer to systemically deliver miRNA-126 into lung cancer cells [ 271 ]. The results showed that this polyplex could efficiently deliver miRNA-126 and inhibit tumor growth in vivo [ 271 ]. PLGA NPs could increase their miRNA encapsulation efficiency by preparing with positively charged molecules like PEI or chitosan [ 272 , 273 ].…”

Chitosan-Based Nanoparticles for Nucleic Acid Delivery: Technological Aspects, Applications, and Future Perspectives

“…Many researchers have reported certain reactions to introduce extra hydrophilic or hydrophobic groups onto the chitosan macromolecules, depending on the application. Several ligands have been utilized, such as glutathione [ 80 ], galactose [ 75 , 81 ], mannose [ 82 ], aptamers [ 83 , 84 ], folic acid [ 85 , 86 ], RGD [ 87 ], and REDV peptides [ 88 , 89 , 90 ], to chemically modify the side groups of chitosan for specific cell targeting. The PEGylation of chitosan is a common strategy utilized for the increase in hydrophilicity, stability, and bioavailability, the avoidance of opsonization, and the reduction in toxicity [ 91 , 92 ].…”

Chitosan Based MicroRNA Nanocarriers

“…Moreover, surface functionalization of chitosan NPs became a valid option to investigate active targeting ensuring better uptake and higher transfection efficiency. Ligands such as REDV peptide in the works of Zhou et al [39,54,55], RGD peptide [56], aptamers [33,57], folic acid [58,59], galactose [24,60], mannose [61], and glutathione [50] have all been investigated within the scope of CS/miR NPs. Most studies were concerning active targeting against cancer cells, however, Pereira et al investigated the use of lactoferrin and stearic acid to enhance the brain targeting ability of their CS nanoplexes to treat Alzheimer's disease [62].…”