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    Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery

    Access Status
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    Authors
    Ichimizu, S.
    Watanabe, H.
    Maeda, H.
    Hamasaki, K.
    Nakamura, Y.
    Chuang, Victor
    Kinoshita, R.
    Nishida, K.
    Tanaka, R.
    Enoki, Y.
    Ishima, Y.
    Kuniyasu, A.
    Kobashigawa, Y.
    Morioka, H.
    Futaki, S.
    Otagiri, M.
    Maruyama, T.
    Date
    2018
    Type
    Journal Article
    
    Metadata
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    Citation
    Ichimizu, S. and Watanabe, H. and Maeda, H. and Hamasaki, K. and Nakamura, Y. and Chuang, V. and Kinoshita, R. et al. 2018. Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery. Journal of Controlled Release. 277: pp. 23-34.
    Source Title
    Journal of Controlled Release
    DOI
    10.1016/j.jconrel.2018.02.037
    ISSN
    0168-3659
    School
    School of Pharmacy and Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/67803
    Collection
    • Curtin Research Publications
    Abstract

    © 2018 Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA. Among the CPPs evaluated, a cyclic polypeptide composed of D-dodecaarginines, palmitoyl-cyclic-(D-Arg) 12 was the most effective for facilitating the cellular uptake of HSA by HeLa cells. Such a superior cell-penetrating capability is primarily mediated by macropinocytosis. The effect of the CPP on pharmacological activity was examined using three drugs loaded in HSA via three different methods: a) an HSA-paclitaxel complex, b) an HSA-doxorubicin covalent conjugate and c) an HSA-thioredoxin fusion protein. The results showed that cell-penetrating efficiency was increased with a corresponding and significant enhancement in pharmacological activity. In conclusion, palmitoyl-cyclic-(D-Arg) 12 /HSA is a versatile cell-penetrating drug delivery system with great potential for use as a nano-carrier for a wide diversity of pharmaceutical applications.

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