title: Synthesis and antitumor activity of novel thermosensitive platinum(II)-cyclotriphosphazene conjugates.
abstract: Thermosensitive cyclotriphosphazenes bearing alkoxy poly(ethylene glycol) and amino acid esters as side groups could be functionalized to chelate the antitumor (diamine)platinum(II) moiety through the dicarboxylate group of the amino acid substituent on the cyclic phosphazene ring. Surprisingly, like the precursor cyclotriphosphazenes, these (diamine)platinum(II)-cyclotriphosphazene conjugates were also found to exhibit variable lower critical solution temperatures (LCST) in the wide range of 12 to 92 degrees C. Furthermore, the present conjugates have shown outstanding in vitro and in vivo antitumor activities due to controlled release of the antitumor (diamine)platinum(II) moiety with hydrolytic degradation of the phosphazene ring. A few of these conjugates have shown LCSTs below body temperature, and it has been shown from a model animal experiment that the conjugates with a LCST below body temperature may be applied to local drug delivery by direct intratumoral injection.
authors.affiliation: Division of Life Science, Korea Institute of Science & Technology, 130-650 Seoul, South Korea.
authors.forename: Soo-Chang
authors.initials: SC
authors.lastname: Song
authors.forename: Sang Beom
authors.initials: SB
authors.lastname: Lee
authors.forename: Bae Hoon
authors.initials: BH
authors.lastname: Lee
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Ha
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001831:Body Temperature; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009943:Organophosphorus Compounds; D009944:Organoplatinum Compounds