Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery
dc.contributor.author | Ichimizu, S. | |
dc.contributor.author | Watanabe, H. | |
dc.contributor.author | Maeda, H. | |
dc.contributor.author | Hamasaki, K. | |
dc.contributor.author | Nakamura, Y. | |
dc.contributor.author | Chuang, Victor | |
dc.contributor.author | Kinoshita, R. | |
dc.contributor.author | Nishida, K. | |
dc.contributor.author | Tanaka, R. | |
dc.contributor.author | Enoki, Y. | |
dc.contributor.author | Ishima, Y. | |
dc.contributor.author | Kuniyasu, A. | |
dc.contributor.author | Kobashigawa, Y. | |
dc.contributor.author | Morioka, H. | |
dc.contributor.author | Futaki, S. | |
dc.contributor.author | Otagiri, M. | |
dc.contributor.author | Maruyama, T. | |
dc.date.accessioned | 2018-05-18T07:59:44Z | |
dc.date.available | 2018-05-18T07:59:44Z | |
dc.date.created | 2018-05-18T00:22:55Z | |
dc.date.issued | 2018 | |
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. | |
dc.identifier.uri | http://hdl.handle.net/20.500.11937/67803 | |
dc.identifier.doi | 10.1016/j.jconrel.2018.02.037 | |
dc.description.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. | |
dc.publisher | Elsevier | |
dc.title | Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery | |
dc.type | Journal Article | |
dcterms.source.volume | 277 | |
dcterms.source.startPage | 23 | |
dcterms.source.endPage | 34 | |
dcterms.source.issn | 0168-3659 | |
dcterms.source.title | Journal of Controlled Release | |
curtin.department | School of Pharmacy and Biomedical Sciences | |
curtin.accessStatus | Fulltext not available |
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