Cationic Oligopeptide-Functionalized Mitochondria Targeting Sequence Show Mitochondria Targeting and Anticancer Activity

• Published in: Macromolecular research Vol. 27; no. 11; pp. 1071 - 1080
• Main Authors: Bae, Yoonhee, Joo, Chanyang, Kim, Goo-Young, Ko, Kyung Soo, Huh, Kang Moo, Han, Jin, Choi, Joon Sig
• Format: Journal Article
• Language: English
• Published: Seoul The Polymer Society of Korea 01.11.2019; Springer Nature B.V; 한국고분자학회
• Subjects: Anticancer properties; Cancer; Cations; Cell death; Characterization and Evaluation of Materials; Chemical compounds; Chemistry; Chemistry and Materials Science; Complex Fluids and Microfluidics; Drug delivery systems; Mitochondria; Nanochemistry; Nanotechnology; Pharmacology; Physical Chemistry; Polymer Sciences; Soft and Granular Matter; Spheroids; Toxicity; Two dimensional models; 고분자공학; Mitochondria targeting; R; MTS-H; anticancer activity; 3D spheroids
• ISSN: 1598-5032; 2092-7673
• DOI: 10.1007/s13233-019-7153-x

Mitochondrial drug delivery systems require development of highly selective mitochondria-targeting carriers. In this study, we report that mitochondria targeting sequence (MTS)-hybrid cationic oligopeptide, MTS-H 3 R 9 , shows the dual role of a mitochondria targeting vector along with anticancer effect for cancer therapy. In cytotoxicity assays, MTS-H 3 R 9 was shown to be more effective than MTS. MTS-H 3 R 9 showed significant cell penetration and internalization activity compared to that of MTS along with more efficient escape from lysosome to the cytosol. We showed efficient targeting of MTS-H 3 R 9 to mitochondria in HeLa cell line. Furthermore, we exhibited anticancer agent properties that mitochondrial-accumulated MTS-H 3 R 9 caused cell death by reactive oxygen species generation and loss of mitochondrial membrane potential. MTS-H 3 R 9 exhibited dramatically increased anticancer activity in 3D spheroids as well as in a 2D culture model. We demonstrated that MTS-H 3 R 9 provides dual potentials both as a vehicle for targeted delivery and as a cancer treatment agent for therapeutic applications.