A new amphiphilic poly(organophosphazene) was synthesized by stepwise nucleophilic substitutions with a hydrophilic methoxy poly(ethylene glycol) with an average molecular weight of 350 (MPEG350) and a hydrophobic glycyl-L-glutamate as side groups, and then an antitumor (dach)platinum(II) (dach: trans-(+/-)-1,2-diaminocyclohexane) moiety was conjugated to the polymer using the dipeptide as a spacer. This polymeric platinum conjugate was found to be accumulated in the tumor tissue to a remarkably greater extent than in the normal tissue (tumor/tissue ratio >4), probably due to the excellent EPR effect and the long circulating properties of the polymer conjugate (t1/2beta=6.2 h and AUC=4020 nmol h/ml) compared with carboplatin (t1/2beta=0.42 h and AUC=120 nmol h/ml). The polymer conjugate also exhibited high in vitro cytotoxicity comparable to cisplatin against several human tumor cells tested.
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