Journal
CHEMICAL SCIENCE
Volume 3, Issue 6, Pages 2083-2087Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2sc01086k
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Funding
- National University of Singapore [R143-000-411-133, R-148-000-129-112]
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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.
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