Pentafluoropropionic Anhydride Functionalized PAMAM Dendrimer as miRNA Delivery Reagent

Abstract

Poly(amidoamine) (PAMAM) dendrimers are good candidates for nucleic acid delivery with their well-defined characteristics. MicroRNA (miRNA) mediated regulation of biological process are also active area of investigation. Fibroblast cells, such as MRC-5, are one of the cell lines used in biological researches due to their hard to transfect nature. In this two-staged study, cystamine core G5 PAMAM dendrimers were synthesized and modified with pentafluoropropionic anhydride (PA) and subsequently tested as miRNA delivery reagent on MRC-5 cells. Effect of fluorination against to naked G5 dendrimer over transfection efficiency was also investigated by molecular docking and quantitative structure-activity relationship (QSAR) calculations. Structural characterization of the synthesized dendrimers was verified by spectroscopic techniques. Gel retardation assay, particle size and transmission electron microscopy results demonstrated polyplex formation ability of fluorinated dendrimers with miRNA at nanoscale level. Zeta potential values indicated non-aggregation and increased stability of the polyplexes. Prepared polyplexes with fluorinated dendrimer showed over 90% cell viability and transfection efficiency. In silico calculations confirmed the stable complexation with miRNA and smooth penetration capability into the cell.