Platinum(iv) prodrugs entrapped within multiwalled carbon nanotubes: Selective release by chemical reduction and hydrophobicity reversal

Abstract

Platinum-based anticancer drugs constitute some of most effective chemotherapeutic regimes, but they are limited by high toxicities and severe side-effects arising from premature aquation and non-specific interactions. Macromolecular delivery agents can be used to shield platinum drugs from adventitious binding and as a platform to attach targeting groups, as a strategy to mitigate some of these limitations. An approach was conceived to utilise carbon nanotubes as a protective shell for stable platinum(iv) prodrugs entrapped within its inner cavities. An inert and strongly hydrophobic platinum(iv) complex was designed for entrapment within multiwalled carbon nanotubes via hydrophobic-hydrophobic interactions. Upon chemical reduction, the drug was converted to its cytotoxic and hydrophilic form and released from the carrier, via a drastic reversal in hydrophobicity, for DNA-binding. This simple method of hydrophobic entrapment and controlled release by chemical reduction and hydrophobicity reversal, exploiting the Pt(iv) scaffold as a prodrug, could form the basis of other delivery strategies for targeted delivery of platinum drugs into cancer cells. © 2012 The Royal Society of Chemistry.