Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery
|dc.identifier.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.|
© 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.
|dc.title||Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery|
|dcterms.source.title||Journal of Controlled Release|
|curtin.department||School of Pharmacy and Biomedical Sciences|
|curtin.accessStatus||Fulltext not available|
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