Cell-penetrating chitosan/doxorubicin/TAT conjugates for efficient cancer therapy

Authors

  • Jue-Yeon Lee,

    1. Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, Seoul, Korea
    2. Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, Seoul, Korea
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  • Young-Suk Choi,

    1. Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, Seoul, Korea
    2. Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, Seoul, Korea
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  • Jin-Sook Suh,

    1. Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, Seoul, Korea
    2. Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, Seoul, Korea
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  • Young-Min Kwon,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
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  • Victor C. Yang,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
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  • Seung-Jin Lee,

    1. Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul, South Korea
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  • Chong-Pyoung Chung,

    1. Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, Seoul, Korea
    2. Department of Periodontology, School of Dentistry, Seoul National University, Seoul, Korea
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  • Yoon-Jeong Park

    Corresponding author
    1. Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, Seoul, Korea
    2. Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, Seoul, Korea
    • Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, Seoul, Korea
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    • Tel: 82-2-740-8651, Fax: 82-2-744-8732


Abstract

In this study, a cell-penetrating peptide, the transactivating transcriptional factor (TAT) domain from HIV, was linked to a chitosan/doxorubicin (chitosan/DOX) conjugate to form a chitosan/DOX/TAT hybrid. The synthesized chitosan/DOX/TAT conjugate showed a different intracellular distribution pattern from a conjugate without TAT. Unlike both free DOX and the conjugate without TAT, the chitosan/DOX/TAT conjugate was capable of efficient cell entry. The chitosan/DOX/TAT conjugate was found to be highly cytotoxic, with an IC50 value of approximately 480 nM, 2 times less than that of chitosan/DOX (980 nM). The chitosan/DOX/TAT provided decreases in tumor volume of 77.4 and 57.5% compared to free DOX and chitosan/DOX, respectively, in tumor-bearing mice. Therefore, this study suggests that TAT-mediated chitosan/DOX conjugate delivery is effective in slowing tumor growth.

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