Cell-Selective Delivery of MicroRNA with a MicroRNA-Peptide Conjugate Nanocomplex.

Targeted delivery of microRNA (miRNA) into specific cells has been regarded as an efficient strategy to enhance miRNA-targeted therapeutics. However, concurrent delivery of therapeutic miRNAs into different target cells that is conducive to multi-target therapy is still underdeveloped. Here, we report a novel strategy for cell-selective delivery of miRNA into different target cells by using miRNA nanocomplexes (MINRCs) formed by miRNA with peptide conjugates. The peptide conjugates comprised a cationic cell-penetrating peptide nona-arginine and a targeting ligand that is cyclic RGD or folic acid. Upon mixing in buffer, the peptide conjugates and miR-34a readily formed two MINRCs, respectively. These two MINRCs facilitated the targeted delivery of miR-34a into RGD receptor-positive U87MG cells or folate receptor-positive HeLa cells via ligand-receptor interaction. We also demonstrated that co-incubation of these two MINRCs with U87MG and HeLa cells led to cell-selective delivery of miR-34a.