Redox double-switch cancer theranostics through Pt(iv) 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.