2000年
Cancer cell-targeted drug delivery utilizing oligopeptide transport activity
International Journal of Cancer
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- 巻
- 88
- 号
- 2
- 開始ページ
- 274
- 終了ページ
- 280
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1002/1097-0215(20001015)88:2<274::AID-IJC20>3.0.CO;2-5
To study the drug delivery to tumor by utilization of an oligopeptide transport activity, we examined the accumulation of dipeptides and the peptide-mimetic anti-cancer drug, bestatin, a substrate of oligopeptide transporter PepTI. Firstly, we established HeLa cells stably expressing human peptide transporter (hPepTI) (HeLa-hPepTI). Secondly, we constructed an experimental model by inoculation of HeLa-hPepTI cells subcutaneously into Balb/c nu/nu mice to demonstrate the contribution of PepTI to the tissue-selective drug delivery. The accumulations of a hydrolysis-resistant dipeptide [3H]carnosine and bestatin in solid tumors formed by HeLa-hPepTI or HeLa-pcDNA3, which are transfected with vector DNA (pcDNA3) were measured. After I.V. administration, tissue-to-plasma concentration ratios (K(p)) of both compounds, in HeLa-hPepTI tumor was significantly greater than that of [14C]inulin, a marker for extracellular fluid space, those of dipeptides in muscle, or those in HeLa-pcDNA3 tumor. Furthermore, bestatin exhibited growth inhibition of HeLa-hPepTI in vitro. In vivo, repeated oral administration of bestatin for 28 days suppressed the growth of HeLa-hPepTI tumor specifically. When HT-1080 cells, which may naturally express oligopeptide transport activity, were transplanted, K(p) of [3H]carnosine was significantly increased n comparison with that in muscle. In addition, oligopeptide transport activities among various human cell lines were examined. These results provide the first demonstration for the selective delivery of oligopeptides to tumors by specific oligopeptide transport activity. (C) 2000 Wiley-Liss, Inc.
- リンク情報
- ID情報
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- DOI : 10.1002/1097-0215(20001015)88:2<274::AID-IJC20>3.0.CO;2-5
- ISSN : 0020-7136
- PubMed ID : 11004680
- SCOPUS ID : 0033813664