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HPMA-copolymer conjugates targeted to tumor endothelium using synthetic oligopeptides
R Pola, M Studenovsky, M Pechar, K Ulbrich, O Hovorka, D Vetvicka, B Rihova
Language English Country Great Britain
Document type Research Support, Non-U.S. Gov't
NLK
Medline Complete (EBSCOhost)
from 2002-02-01 to 1 year ago
- MeSH
- Acrylamides chemistry MeSH
- Apoptosis drug effects MeSH
- Cell Line MeSH
- Time Factors MeSH
- Endothelium, Vascular metabolism pathology MeSH
- Microscopy, Fluorescence MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplasms drug therapy pathology MeSH
- Oligopeptides administration & dosage pharmacokinetics chemical synthesis MeSH
- Neovascularization, Pathologic MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Synthesis and characterization of N-(2-hydroxypropyl)methacrylamide (HPMA)-copolymer-based drug carriers targeted on specific receptors in the membrane of endothelial cells by oligopeptides (GRGDG, cyclo(RGDfK), and PHSCN) are described in this study. The copolymers containing targeting oligopeptides bound to the polymer via dodeca(ethylene glycol) spacer showed a receptor-specific time-dependent uptake with selected endothelial cell lines. The polymers were labeled with a fluorescent dye to enable monitoring of the interaction of the polymer conjugate with cells using fluorescence microscopy. Cellular uptake and apoptosis induction have been studied in vitro using various cell lines (EA.hy926, 3T3, SW620, and EL4). In vivo accumulation of the conjugate specifically targeted with cyclo(RGDfK) within the tumor vasculature was detected using fluorescence intravital microscopy in mice. The conjugate targeted by cyclo(RGDfK) was accumulated preferentially in the periphery of the growing tumor suggesting that the cyclo(RGDfK) peptide targets the polymer conjugate to the site of neoangiogenesis, rather than to the tumor mass.
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- $a Synthesis and characterization of N-(2-hydroxypropyl)methacrylamide (HPMA)-copolymer-based drug carriers targeted on specific receptors in the membrane of endothelial cells by oligopeptides (GRGDG, cyclo(RGDfK), and PHSCN) are described in this study. The copolymers containing targeting oligopeptides bound to the polymer via dodeca(ethylene glycol) spacer showed a receptor-specific time-dependent uptake with selected endothelial cell lines. The polymers were labeled with a fluorescent dye to enable monitoring of the interaction of the polymer conjugate with cells using fluorescence microscopy. Cellular uptake and apoptosis induction have been studied in vitro using various cell lines (EA.hy926, 3T3, SW620, and EL4). In vivo accumulation of the conjugate specifically targeted with cyclo(RGDfK) within the tumor vasculature was detected using fluorescence intravital microscopy in mice. The conjugate targeted by cyclo(RGDfK) was accumulated preferentially in the periphery of the growing tumor suggesting that the cyclo(RGDfK) peptide targets the polymer conjugate to the site of neoangiogenesis, rather than to the tumor mass.
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