Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads*
Synthetic delivery systems have great potential for overcoming problems associated with systemic toxicity that accompanies chemotherapy, including platinum-based treatment. Polyvalent oligonucleotide gold nanoparticle conjugates (DNA-AuNPs) have appealing properties for drug delivery applications, including high cellular uptake in a variety of cell types, no demonstrated toxicity inherent to the conjugate, and resistance to enzymatic degradation. Pt(IV) complexes provide an attractive alternative to Pt(II) compounds because their inertness results in fewer side effects. Pt(IV) complexes are reduced in the intracellular milieu to yield the cytotoxic Pt(II) species through reductive elimination of axial ligands. This chapter combines the properties of DNA-AuNPs and Pt(IV) prodrugs into a single agent for drug delivery. It demonstrates that a Pt(IV) complex, which is otherwise inactive, can be made active against several cancer cell lines when attached to DNA-AuNPs.