Peptide-doxorubicin conjugates specifically degraded by matrix metalloproteinases expressed from tumor
- Authors
- Lee, Gee Young; Song, Ji-hye; Kim, Sang Yoon; Park, Kyeongsoon; Byun, Youngro
- Issue Date
- May-2006
- Publisher
- WILEY
- Keywords
- matrix metalloproteinases; peptide-drug conjugates; doxorubicin; tumor targeting
- Citation
- DRUG DEVELOPMENT RESEARCH, v.67, no.5, pp 438 - 447
- Pages
- 10
- Journal Title
- DRUG DEVELOPMENT RESEARCH
- Volume
- 67
- Number
- 5
- Start Page
- 438
- End Page
- 447
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/50336
- DOI
- 10.1002/ddr.20092
- ISSN
- 1098-2299
0272-4391
- Abstract
- Specific peptide-doxorubicin conjugates were developed for targeting matrix metalloproteinases (MMPs) expressed from tumors. The pepticle-doxorubicin conjugates were designed to be cleaved by MMP-2 and MMP-9 in order that doxorubicin or the active form that acts as an anticancer agent was released free from the peptide fragment at the tumor site. Three types of peptide-doxorubicin conjugates were synthesized using the peptides: GPLG (Gly-Pro-Leu-Gly), GPLGV (Gly-Pro-Leu-Gly-Val), and GPLGPAG (Gly-Pro-Leu-Gly-Pro-Ala-Gly). The synthesized pepticle-doxorubicin conjugates were characterized for their degradation behavior and bioactivity in vitro, and their antitumoral activity was assessed using the Lewis lung carcinoma (LLC) model, which expresses MMP-2 and MMP-9. After incubation with active MMP-2 for 24h, GPLG-doxorubicin was barely degraded, whereas GPLGV-doxorubicin and GPLGPAG-doxorubicin were considerably degraded by active MMP-2. Consequently, all pepticle-doxorubicin conjugates had significantly low cytotoxicity compared to doxorubicin, but tumor growth suppression was exhibited only by GPLGV-doxorubicin and GPLGPAG-doxorubicin. The tumor growth suppression by the two conjugates was higher compared to control, although it did not exceed the suppression level shown by doxorubicin. The low toxicity exhibited by pepticle-doxorubicin conjugates resulted in only slight body weight loss in mice, whereas doxorubicin greatly reduced body weight and induced severe side effects. Therefore, we propose MMPs-specific peptide-doxorubicin conjugates in targeting anti-cancer drug delivery that could reduce systemic toxicities.
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Collections - College of Biotechnology & Natural Resource > Department of Systems Biotechnology > 1. Journal Articles
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