Redox double-switch cancer theranostics through Pt() functionalised manganese dioxide nanostructures

Manganese dioxide (MnO 2 )-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO 2 nanostructures with Pt( iv ) prodrugs as redox- (and thus TME-) responsive theranostics for cancer therapy, in which the Pt( iv ) complexes act as prodrugs of cisplatin (Pt( ii )), a clinical chemotherapeutic drug. The cytotoxicity of these MnO 2 -Pt( iv ) probes was evaluated in two and three dimensional (2D and 3D) A549 cell models and found to be as effective as active drug cisplatin in 3D models. Moreover, MnO 2 -Pt( iv ) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity ( r 1 ) increasing 136-fold upon treatment with ascorbic acid. This off/ON MR switch was also observed in (2D and 3D) cells in vitro . In vivo MRI experiments revealed that the nanostructures induce a strong and long-lasting T 1 signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO 2 -Pt( iv ) NPs as redox responsive MR theranostics for cancer therapy. A new redox-responsive double-switch cancer theranostic was developed based on Mn nanostructures and a Pt prodrug. The ability of these probes to respond to altered redox states was validated in 2/3D cell models and in a preclinical mouse model.