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Investigation of Intracellular Delivery of NuBCP-9 by Conjugation with Oligoarginines Peptides in MDA-MB-231 Cells

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タイトル: Investigation of Intracellular Delivery of NuBCP-9 by Conjugation with Oligoarginines Peptides in MDA-MB-231 Cells
著者: Wang, Wei / Suga, Tadaharu / Hagimori, Masayori / Kuroda, Naotaka / Fuchigami, Yuki / Kawakami, Shigeru
発行日: 2018年 9月 1日
出版者: 日本薬学会 / Pharmaceutical Society of Japan
引用: Biological and Pharmaceutical Bulletin, 41(9), pp.1448-1455; 2018
抄録: Oligoarginines (Rn) are becoming promising tools for the intracellular delivery of biologically active molecules. NuBCP-9, a peptide that induces apoptosis in B-cell lymphoma 2 (Bcl-2)-expressing cancer cells, has been reported to promote the uptake and non-specific cytotoxicity of R8, also called octaarginine. However, it is unknown whether a similar synergistic effect can be seen with other Rn. In this study, we conjugated NuBCP-9 with various Rn (n=8, 10, 12, 14) to investigate and compare their cellular uptake characteristics. In addition, their non-specific cytotoxicity and apoptosis-inducing abilities were evaluated. We found that NuBCP-9 conjugated with Rn enhanced cellular uptake mainly through clathrin-mediated endocytosis and macropinocytosis, and that the uptake pathways were not different from those used by unconjugated Rn. However, the cytotoxicity study showed that NuBCP-9-R12 and NuBCP-9-R14 conjugates enhanced nonspecific cytotoxicity. We found that NuBCP-9-R10 conjugate had the highest uptake efficiency and induced correspondingly high levels of apoptosis, while resulting in a tolerable degree of non-specific toxicity.
キーワード: B-cell lymphoma 2 (Bcl-2) / Endocytosis / ntracellular delivery / NuBCP-9 / Oligoarginine
URI: http://hdl.handle.net/10069/38602
ISSN: 09186158
DOI: 10.1248/bpb.b18-00335
権利: © 2018 The Pharmaceutical Society of Japan.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:050 学術雑誌論文

引用URI : http://hdl.handle.net/10069/38602



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