Conjugation between maleimide-containing Pt(IV) prodrugs and furan or furan-containing drug delivery vectors via Diels-Alder cycloaddition

Pt(IV) complexes are considered to act as antitumor prodrugs and their in vivo activity can be improved exploiting drug targeting and delivery strategies. With a view to such applications, the maleimide-containing ligand 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid was used to produce the cisplatin-based Pt(IV) complexes (OC-6-44)-diamminedichlorido(ethanolato)(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetato)platinum(IV) and (OC-6-44)-acetatodiamminedichlorido(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetato)platinum(IV). These complexes underwent Diels-Alder reaction with furan, used as a model molecule to set up the experimental conditions, at ambient temperature up to 50 h, with limited decomposition. Finally, the reaction between the maleimide-containing Pt(IV) complexes and silica nanoparticles decorated with furan were successfully used as a proof-of-concept to demonstrate the clickability of functionalized vectors for drug delivery.