Selective tumor targeting by enhanced permeability and retention effect. Synthesis and antitumor activity of polyphosphazene-platinum (II) conjugates.
Nanosized polyphosphazene-platinum (II) conjugates with a wide range of molecular weight from 24,000 to 115,000 were synthesized to study their tumor selectivity by enhanced permeability and retention (EPR) effect and their antitumor activity. It has been found from biodistribution study that the present polyphosphazene-Pt(II) conjugates exhibit high tumor selectivity by EPR effect with the tumor to tissue ratio (TTR) from 3.6 to 13 depending on the molecular size. These polymer conjugates have shown excellent in vivo antitumor activity against both murine and human cancer cell lines. In particular, xenograft trials of the conjugates have shown outstanding tumor inhibition effect on the stomach cancer cell line, YCC-3, which is one of the least responsive to the anticancer agents currently in clinical use, although the reason is not clearly explainable yet. The high in vivo activity seems to be attributed to the controlled-release of the antitumor active platinum (II) moiety, [GlyGluPt(dach] (dach=trans-(+/-)-1,2-diaminocyclohexane) from the phosphazene backbone by degradation in aqueous solution.
Jun
Yong Joo
YJ
Department of Chemistry, Division of Nano Science, Ewha Womans University, Seodaemun-Ku, Daehyun-Dong 11-1, Seoul 120-750, Republic of Korea.
Kim
Joo Ik
JI
Jun
Moo Jin
MJ
Sohn
Youn Soo
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D017671:Platinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry*; D013379:Substrate Specificity; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D017671:Platinum Compounds; D011108:Polymers; C108974:poly(phosphazene)