Mitochondrial targeting functional peptides as potential devices for the mitochondrial delivery of a DF-MITO-Porter

Abstract

To achieve mitochondrial therapy, we previously reported on the use of an octaarginine (R8) modified Dual Function (DF)-MITO-Porter for delivering molecules to mitochondria in living cells. In this study, using isolated mitochondria, homogenates and living cells, we evaluated the utility of mitochondrial targeting functional peptides as a ligand for delivering carriers. The S2 peptide modified carrier showed a high mitochondrial targeting activity in homogenates and living cells. In addition, the S2 peptide had a lower cell toxicity compared to R8 modified liposomes. The S2 peptide represents a potentially useful moiety for constructing an efficient and safe mitochondrial delivery system.

Packaging of the Coenzyme Q₁₀ into a Liposome for Mitochondrial Delivery and the Intracellular Observation in Patient Derived Mitochondrial Disease Cells

“…As reported previously, 20) the S2-peptide also efficiently targets mitochondria but has been shown to be less cytotoxic compared to modification with R8-peptide. Figure 7B shows the cellular trafficking of the CoQ 10 -MITO-Porter and the empty MITO-Porter modified with the S2-peptide.…”

“…Stearylated R8 (STR-R8) 19) was obtained from KURABO Industries (Osaka, Japan). STR-S2 (stearyl-Dmt-D-Arg-FK-Dmt-D-Arg-FK-NH 2 , Dmt=2, 6-dimethyltyrosine) 20) was obtained from Toray Research Center (Tokyo, Japan). CoQ 10 was obtained from Wako Pure Chemical Industries, Ltd. (Osaka, Japan).…”

A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting

“…The results presented herein constitute the first report of the use of a mitochondrial RNA aptamer modified nanocarrier system to regulate intracellular trafficking, although lipophilic and cationic peptide-based mitochondrial targeting has been reported in previous studies 12,19,[33][34][35] . In this study, we determined the optimal dual-ligand system for a nanocarrier for achieving efficient cellular uptake and mitochondrial targeting (RP/R8-modified MITO-Porter).…”

Development of a multifunctional envelope-type nano device and its application to nanomedicine

“…More recently, we evaluated the utility of mitochondrial targeting functional peptides as a ligand for delivering carriers using isolated mitochondria, homogenates and living cells [105]. (Fig.…”