Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery
© 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 e...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/67803 |
| _version_ | 1848761662111219712 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Ichimizu, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 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. |
| first_indexed | 2025-11-14T10:35:14Z |
| format | Journal Article |
| id | curtin-20.500.11937-67803 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:35:14Z |
| publishDate | 2018 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-678032018-05-18T08:04:22Z Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery 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. © 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/67803 10.1016/j.jconrel.2018.02.037 Elsevier restricted |
| spellingShingle | 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. Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
| title | Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
| title_full | Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
| title_fullStr | Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
| title_full_unstemmed | Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
| title_short | Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
| title_sort | design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
| url | http://hdl.handle.net/20.500.11937/67803 |