Platinum (IV)-coordinate polymers as intracellular reduction-responsive backbone-type conjugates for cancer drug delivery
Platinum (IV)-coordinate polymers were synthesized by condensation polymerization using diamminedichlorodihydroxyplatinum (DHP) or its dicarboxyl derivative diamminedichlorodisuccinatoplatinum (DSP) as comonomers. Cyclic voltammogram study showed that Pt (IV) in the polymers was much easier reduced to Pt (II), particularly at the acidic pH, than that in the monomer DSP. Thus, these polymers were intracellular reduction-responsive backbone-type polymer conjugates that could be degraded and release Pt (II). These conjugates not only had high and fixed platinum contents (27.7% for P(DSP-EDA) and 29.6% for P(DSP-PA), respectively), but also showed increased cytotoxicity compared with corresponding Pt (IV) monomer DSP toward various tumor cell lines. In vivo, the conjugate showed a longer blood circulation time and better tumor accumulation.
Journal: Biomaterials - Volume 32, Issue 34, December 2011, Pages 9136–9143