A macromolecular prodrug of doxorubicin conjugated to a biodegradable cyclotriphosphazene bearing a tetrapeptide.
A new biodegradable water-soluble phosphazene trimer-doxorubicin conjugate was synthesized, in which equimolar hydrophilic methoxy-poly(ethylene glycol) with a molecular weight of 350 (MPEG350) and a tumor-specific tetrapeptide (Gly-Phe-Leu-Gly) were grafted to cyclotriphosphazene. The present conjugate exhibited cytotoxicity lower than that of free doxorubicin (IC50=0.10 microM) but a reasonably higher in vitro cytotoxicity (IC50=1.1 microM) against the leukemia L1210 cell line probably due to its enzymatically controlled release.
Department of Chemistry, Division of Nano Science, Ewha Womans University, Seoul 120-750, South Korea.
Jin Kyu
JK
Kim
Udaya S
US
Toti
Rita
R
Song
Youn Soo
YS
Sohn
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D001673:Biodegradation, Environmental; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D009570:Nitriles / Q000737:chemistry* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017553:Phosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011355:Prodrugs; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; C504380:Gly-Phe-Leu-Gly; D009570:Nitriles; D009842:Oligopeptides; D017553:Phosphorus Compounds; D011355:Prodrugs; C068226:cyclotriphosphazene ester; D011092:Polyethylene Glycols; D004317:Doxorubicin