The role of manganese-based MRI contrast agents for cancer theranostics: Where do we stand in 2025?

Magnetic resonance imaging (MRI) guidance in the realm of anticancer therapy is crucial to visualize the spread of tumors in deep tissues, accumulate the therapeutics, and trigger them for precise therapy. Recent studies bridge this gap by integrating MRI contrast agents (CAs) with different therapeutic regimes for a better outcome. In this context, manganese-based materials hold great potential owing to their T₁/T2 dual-modal MR-relaxation, less toxicity, and other therapeutic capabilities such as chemodynamic therapy, immunotherapy, etc., which have gained increasing interest among researchers and medical professionals. This work offers a timely update on the last three years for Mn-based MRI-guided theranostic applications, including chemodynamic therapy, chemotherapy, photo therapies, sonodynamic therapy, and radiotherapy against cancer. Further, several combinatory therapies and surgical intersections have also been summarized in the light of MRI guidance. The design rationale of these Mn-based agents has been discussed to understand the existing challenges and plausible outcomes shortly. Herein, we deep dive into the stimulus-based probes including pH, temperature, etc. to show the unexplored potential of Mn-complexes in this domain. This state-of-the-art review will guide innovations in Mn-based CAs to expedite safer anticancer theranostic modules for clinical translation.