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.
雑誌名
Biological and Pharmaceutical Bulletin
巻
41
号
9
ページ
1448 - 1455
発行年
2018-09-01
出版者
日本薬学会
出版者別言語
Pharmaceutical Society of Japan
ISSN
09186158
EISSN
13475215
DOI
10.1248/bpb.b18-00335
権利
c 2018 The Pharmaceutical Society of Japan.
著者版フラグ
publisher
引用
Biological and Pharmaceutical Bulletin, 41(9), pp.1448-1455; 2018
Investigation of Intracellular Delivery of NuBCP-9 by Conjugation with Oligoarginines Peptides in MDA-MB-231 Cells
BPBul41_1448.pdf
(3.28MB)
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