The dual-role of Pt(iv) complexes as active drug and crosslinker for micelles based on β-cyclodextrin grafted polymer†
With a combination of RAFT and click chemistry an amphiphilic block copolymer with poly(ethylene glycol) methyl ether methacrylate (POEGMEMA) as hydrophilic block and poly(propargyl methacrylate) (PMA) as hydrophobic block has been successfully synthesized. To this, 6-azide-6-deoxy-β-cyclodextrin (N3-β-CD) was clicked creating a hosting environment for a hydrophobic small molecule platinum pro-drug. Oxoplatin, the oxidized version of cisplatin, has been modified on its axial ligand introducing cholic acid groups through esterification. This modified cisplatin forms a host–guest complex with β-cyclodextrin that has been characterised via NMR spectroscopy. The host–guest interaction that the drug established with the β-cyclodextrin grafted copolymer drove the self-assembly into nanoparticles of a diameter of 266 nm able to physical encapsulate the platinum-based drug. In the presence of ascorbic acid, 70% of the pro-drug is released over a period of 24 h. Cytotoxicity assays on ovarian cancer cells show that the polymer carrier improves the cytotoxicity of the platinum pro-drug. The IC50 value decreases from 37.7 μM with the pro-drug to 20.4 μM when the pro-drug is encapsulated into the polymer carrier. This is due to the fact that the uptake of the polymer carrier is up to 6 fold higher than the significantly smaller pro-drug by itself.