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

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Abstract

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-H3R9, shows the dual role of a mitochondria targeting vector along with anticancer effect for cancer therapy. In cytotoxicity assays, MTS-H3R9 was shown to be more effective than MTS. MTS-H3R9 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-H3R9 to mitochondria in HeLa cell line. Furthermore, we exhibited anticancer agent properties that mitochondrial-accumulated MTS-H3R9 caused cell death by reactive oxygen species generation and loss of mitochondrial membrane potential. MTS-H3R9 exhibited dramatically increased anticancer activity in 3D spheroids as well as in a 2D culture model. We demonstrated that MTS-H3R9 provides dual potentials both as a vehicle for targeted delivery and as a cancer treatment agent for therapeutic applications.

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Authors and Affiliations

  1. Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, 34134, Korea

    Joon Sig Choi

  2. Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, 47392, Korea

    Yoonhee Bae & Jin Han

  3. Department of Internal Medicine, Sanggye Paik Hospital, Cardiovascular and Metabolic Disease Center, Inje University, Seoul, 01757, Korea

    Kyung Soo Ko

  4. Department of Biology and Clinical Pharmacology, R&D Center, Samyang Biopharmaceuticals Corporation, Seongnam, 13480, Korea

    Goo-Young Kim

  5. Department of Polymer Science and Engineering, Chungnam National University, Daejeon, 34134, Korea

    Chanyang Joo & Kang Moo Huh

Authors
  1. Yoonhee Bae
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  2. Chanyang Joo
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  3. Goo-Young Kim
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  4. Kyung Soo Ko
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  5. Kang Moo Huh
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  6. Jin Han
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  7. Joon Sig Choi
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Correspondence to Jin Han or Joon Sig Choi.

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Acknowledgments: This work was supported by grant from Basic Science Research Program through the National Research Foundation of Korea (NRF-2016R1D1A1A09917141) and by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2016M3A9B4919639). This work was also supported by the Priority Research Centers Program (2010-0020224).

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Bae, Y., Joo, C., Kim, GY. et al. Cationic Oligopeptide-Functionalized Mitochondria Targeting Sequence Show Mitochondria Targeting and Anticancer Activity. Macromol. Res. 27, 1071–1080 (2019). https://doi.org/10.1007/s13233-019-7153-x

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  • DOI: https://doi.org/10.1007/s13233-019-7153-x

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