Peptide-doxorubicin conjugates specifically degraded by matrix metalloproteinases expressed from tumor
DC Field | Value | Language |
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dc.contributor.author | Lee, Gee Young | - |
dc.contributor.author | Song, Ji-hye | - |
dc.contributor.author | Kim, Sang Yoon | - |
dc.contributor.author | Park, Kyeongsoon | - |
dc.contributor.author | Byun, Youngro | - |
dc.date.accessioned | 2021-10-18T06:40:26Z | - |
dc.date.available | 2021-10-18T06:40:26Z | - |
dc.date.issued | 2006-05 | - |
dc.identifier.issn | 1098-2299 | - |
dc.identifier.issn | 0272-4391 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/50336 | - |
dc.description.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. | - |
dc.format.extent | 10 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | WILEY | - |
dc.title | Peptide-doxorubicin conjugates specifically degraded by matrix metalloproteinases expressed from tumor | - |
dc.type | Article | - |
dc.identifier.doi | 10.1002/ddr.20092 | - |
dc.identifier.bibliographicCitation | DRUG DEVELOPMENT RESEARCH, v.67, no.5, pp 438 - 447 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000240724400003 | - |
dc.citation.endPage | 447 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 438 | - |
dc.citation.title | DRUG DEVELOPMENT RESEARCH | - |
dc.citation.volume | 67 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | matrix metalloproteinases | - |
dc.subject.keywordAuthor | peptide-drug conjugates | - |
dc.subject.keywordAuthor | doxorubicin | - |
dc.subject.keywordAuthor | tumor targeting | - |
dc.subject.keywordPlus | ANTITUMOR EFFICACY | - |
dc.subject.keywordPlus | GELATINASES | - |
dc.subject.keywordPlus | INVASION | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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