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

Manganese dioxide (MnO₂)-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO₂ 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 MnO₂-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, MnO₂-Pt(IV) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity (r₁) 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 T₁ signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO₂-Pt(IV) NPs as redox responsive MR theranostics for cancer therapy.