Gallic acid-mitochondria targeting sequence-H(3)R(9) induces mitochondria-targeted cytoprotection

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H(3)R(9) exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H(3)R(9) showed a better rescue action compared to that of MTS-H(3)R(9). GA-MTS-H(3)R(9) dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H(3)R(9) towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTS-H(3)R(9) alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H(3)R(9) showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H(3)R(9). We showed that GA-MTS-H(3)R(9) can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.