Platinum(IV) cisplatin derivative trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV) has an enhanced therapeutic index compared to cisplatin for the treatment of non-small cell lung cancer

•A platinum(IV) cisplatin derivative was prepared and characterized.•It is much more toxic toward non-small cell lung cancer cells than is cisplatin.•It has an improved therapeutic index compared to cisplatin.•The reduced complex binds to DNA in a manner similar to that of cisplatin.•It can be incorporated into mesoporous silica nanoparticles for tumor targeting.

Lung cancer is the leading cause of cancer-related death in the United States, and non-small cell lung cancer (NSCLC) the most common type. Platinum (Pt) anticancer agents, such as cisplatin, remain a mainstay in the clinic; however, these agents are not tumor-specific and, thus, the patient experiences negative side-effects. We here prepare trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV) and demonstrate that it is greater than 50-fold more toxic toward NSCLC cells than is cisplatin. Furthermore, it has a much improved therapeutic index. This Pt(IV) complex binds to DNA in a manner similar to that of cisplatin, and can be incorporated into mesoporous silica nanoparticles for fine-controlled release and the targeting of tumors.

Graphical abstractTrans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV) is much more toxic toward non-small cell lung cancer (NSCLC) cells than is cisplatin, and has an improved therapeutic index. This Pt(IV) complex binds to DNA in a similar manner to that of cisplatin, and can be incorporated into mesoporous silica nanoparticles.Figure optionsDownload full-size imageDownload as PowerPoint slide