Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 23-34 |
| Number of pages | 12 |
| Journal | Journal of Controlled Release |
| Volume | 277 |
| DOIs | |
| Publication status | Published - 2018 May 10 |
| Externally published | Yes |
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Keywords
- Albumin fusion technology
- Cell-penetrating peptide
- Drug binding
- Human serum albumin
- Macropinocytosis
- Palmitate high affinity binding site
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery. / Ichimizu, Shota; Watanabe, Hiroshi; Maeda, Hitoshi; Hamasaki, Keisuke; Nakamura, Yuka; Chuang, Victor Tuan Giam; Kinoshita, Ryo; Nishida, Kento; Tanaka, Ryota; Enoki, Yuki; Ishima, Yu; Kuniyasu, Akihiko; Kobashigawa, Yoshihiro; Morioka, Hiroshi; Futaki, Shiro; Otagiri, Masaki; Maruyama, Toru.
In: Journal of Controlled Release, Vol. 277, 10.05.2018, p. 23-34.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery
AU - Ichimizu, Shota
AU - Watanabe, Hiroshi
AU - Maeda, Hitoshi
AU - Hamasaki, Keisuke
AU - Nakamura, Yuka
AU - Chuang, Victor Tuan Giam
AU - Kinoshita, Ryo
AU - Nishida, Kento
AU - Tanaka, Ryota
AU - Enoki, Yuki
AU - Ishima, Yu
AU - Kuniyasu, Akihiko
AU - Kobashigawa, Yoshihiro
AU - Morioka, Hiroshi
AU - Futaki, Shiro
AU - Otagiri, Masaki
AU - Maruyama, Toru
PY - 2018/5/10
Y1 - 2018/5/10
N2 - 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.
AB - 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.
KW - Albumin fusion technology
KW - Cell-penetrating peptide
KW - Drug binding
KW - Human serum albumin
KW - Macropinocytosis
KW - Palmitate high affinity binding site
UR - http://www.scopus.com/inward/record.url?scp=85043996259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043996259&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2018.02.037
DO - 10.1016/j.jconrel.2018.02.037
M3 - Article
C2 - 29530390
AN - SCOPUS:85043996259
VL - 277
SP - 23
EP - 34
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -