A Carrier-free Nanoparticle Based On Platinum(?)Prodrug Enhances Cellular Uptake,Cytotoxicity And Anti-tumor Ability In Vivo

Flurbiprofen,a hydrophobic COX inhibitor,was coordinated axially with oxoplatin to form a new conjugate cis,cis,trans-[Pt(IV)(NH3)2Cl2(flurbiprofen)2].The successful synthesis of this new conjugate was confirmed by 1H,13C and 195Pt NMR respectively.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 spectrum(MS).This conjugate showed markedly higher cytotoxicity on many cancer cell lines than cisplatin,flurbiprofen and physical mixture(mol ratio,cisplatin:flurbiprofen=1:2)of them.This is consistent with the result of apoptosis-inducing assay.This conjugate spontaneously assembled carrier-free nanoparticles in aqueous solution,which was confirmed by DLS,TEM,SEM and AFM,thus facilitateed cellular uptake,markedly improved its cytotoxicity and apoptosis-inducing ability in vitro.The in.vivo antitumor efficiency of Platin-FP nanoparticles was analyzed on SW480 tumor xenograft mice models and the result showed that Platin-FP nanoparticles significantly enhanced the anti-tumor activity at low micromolar concentrations.