A Carrier-Free Nanostructure Based on Platinum(IV) Prodrug Enhances Cellular Uptake and Cytotoxicity

Flurbiprofen, a hydrophobic COX inhibitor, was coordinated axially with oxoplatin to form a new conjugate, <i>cis</i>,<i>cis</i>,<i>trans</i>-[Pt­(IV)­(NH₃)₂Cl₂(flurbiprofen)₂]. The successful synthesis of this new conjugate was confirmed by ¹H, ¹³C, and ¹⁹⁵Pt NMR. The potential of this conjugate being reduced to cisplatin and subsequently exerting its DNA cross-linking ability was verified using cyclic voltammetry (CV), HPLC, and mass spectrometry (MS). This conjugate showed markedly higher cytotoxicity on many cancer cell lines than cisplatin, flurbiprofen, and their physical mixture (mole ratio, cisplatin:flurbiprofen = 1:2). This is consistent with the result of an apoptosis-inducing assay. This conjugate spontaneously assembles carrier-free nanoparticles in aqueous solution, which is confirmed by DLS, TEM, SEM, and AFM, and thus facilitates cellular uptake and markedly improves its cytotoxicity and apoptosis-inducing ability <i>in vitro