α‑Aminoisobutyric Acid-Containing Amphipathic Helical Peptide-Cyclic RGD Conjugation as a Potential Drug Delivery System for MicroRNA Replacement Therapy in Vitro

• Published in: Molecular pharmaceutics Vol. 16; no. 11; pp. 4542 - 4550
• Main Authors: Taniguchi, Kohei, Wada, Shun-ichi, Ito, Yuko, Hayashi, Junsuke, Inomata, Yosuke, Lee, Sang-Woong, Tanaka, Tomohito, Komura, Kazumasa, Akao, Yukihiro, Urata, Hidehito, Uchiyama, Kazuhisa
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 04.11.2019
• Subjects: microRNA; drug delivery system; replacement therapy; cell-penetrating peptide; oligonucleotide therapy
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.9b00680

Replacement therapy with tumor suppressive microRNA (TS-miRNA) might be the next-generation oligonucleotide therapy; however, a novel drug delivery system (DDS) is required. Recently, we developed the cell-penetrating peptide, model amphipathic peptide with α-aminoisobutyric acid (MAP­(Aib)), as a carrier for oligonucleotide delivery to cells. In this study, we examined whether a modified MAP­(Aib) analogue, MAP­(Aib)-cRGD, could be a DDS for TS-miRNA replacement therapy. MIR145-5p, a representative TS-miRNA especially in colorectal cancer, was selected. The MAP­(Aib)-cRGD dose was adjusted for MIR145-5p delivery to cells using peripheral blood mononuclear cells and degradation analysis. AlexaFluor488-labeled MIR145-5p incorporation into cells and negative regulation of MIR145-5p-targeting genes demonstrated MAP­(Aib)-cRGD’s functionality as a miRNA DDS. Treating MIR145-5p with MAP­(Aib)-cRGD also revealed various anticancer effects, such as cell viability, invasion inhibition, and apoptosis induction in WiDr cells. Altogether, these findings suggest that MAP­(Aib)-cRGD could be a DDS for TS-miRNA replacement therapy, but in vivo investigations are required.