Ratiometric delivery of cisplatin and doxorubicin using tumour-targeting carbon-nanotubes entrapping platinum(iv) prodrugs

Abstract

Combination therapy is an effective strategy to enhance the efficacy of single-agent chemotherapy and delay onset of chemoresistance. However, differences in the pharmacokinetic profiles of the drug constituents can complicate the implementation of combination regimens in a clinical setting. Nanomaterials can overcome these limitations by offering a unified platform for targeted and synchronous delivery of multiple drugs, although exact ratiometric loading cannot be assured using conventional encapsulation techniques. An approach was conceived with the goal of delivering exact stoichiometric proportions of cisplatin and doxorubicin against endometrial adenocarcinoma using tumour-targeting multi-walled carbon nanotubes entrapping an inert Pt(IV) prodrug. Activation of the Pt(IV) prodrug after cell entry, synchronously releases molar equivalents of hydrophilic cisplatin and doxorubicin from the hydrophobic confines, thereby achieving ratiometric delivery of these mechanistically-complementary drug entities.