Manganese Ion-Based NanoPlatforms for Tumor Theranostics.

Abstract

Manganese-ion-based nanoparticles have emerged as highly versatile platforms that seamlessly integrate diagnostic and therapeutic functions, enabling precision cancer theranostics. In this review, we discuss manganese-based nanomaterials through a design-oriented framework that connects synthesis, structure, function, application, and limitation. Mainstream preparation strategies, including thermal decomposition, permanganate reduction, hydrothermal/solvothermal synthesis, template-assisted construction, coprecipitation, and mild biomimetic routes, are compared with respect to physicochemical control, Mn activation behavior, scalability, and biomedical suitability. The diagnostic applications of manganese-based nanoplatforms are discussed, including activatable T₁-weighted magnetic resonance imaging (MRI) and multimodal imaging systems, as well as Mn-activated DNAzyme platforms for gene regulation. We further review therapeutic modalities enabled by Mn² ⁺, encompassing chemodynamic therapy (CDT), nanozyme-mediated redox regulation within the tumor microenvironment, stimulus-responsive drug and prodrug delivery, magnetic hyperthermia, and their synergistic combinations. Finally, we critically analyze key biosafety considerations along with current translational challenges and future perspectives for developing clinically viable, image-guided combination cancer therapies based on manganese-ion nanoplatforms.