Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery
| Autor: | Yuka Nakamura, Akihiko Kuniyasu, Yu Ishima, Ryota Tanaka, Ryo Kinoshita, Yuki Enoki, Yoshihiro Kobashigawa, Shiro Futaki, Hitoshi Maeda, Kento Nishida, Keisuke Hamasaki, Hiroshi Morioka, Shota Ichimizu, Masaki Otagiri, Toru Maruyama, Victor Tuan Giam Chuang, Hiroshi Watanabe |
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| Rok vydání: | 2018 |
| Předmět: |
Intracellular Fluid
0301 basic medicine Cell Membrane Permeability Membrane permeability Pharmaceutical Science Serum Albumin Human Cell-Penetrating Peptides 02 engineering and technology Structure-Activity Relationship 03 medical and health sciences Drug Delivery Systems medicine Humans Structure–activity relationship Dose-Response Relationship Drug Chemistry Biological activity 021001 nanoscience & nanotechnology Human serum albumin Fusion protein body regions 030104 developmental biology Drug Design embryonic structures Drug delivery Cell-penetrating peptide Biophysics Nanoparticles 0210 nano-technology HeLa Cells medicine.drug Conjugate |
| Zdroj: | Journal of Controlled Release. 277:23-34 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2018.02.037 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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