Mn²⁺ nanoreactors: Diagnostic and therapeutic applications in tumor-targeted MRI and microenvironment remodeling

Cancer, as a life-threatening disease posing severe risks to human health, faces challenges in improving diagnostic and therapeutic efficiency due to the heterogeneous and dynamically complex nature of tumor microenvironment (TME). Conventional imaging modalities, gadolinium-enhanced magnetic resonance imaging (MRI), for instance, exhibiting inherent limitations including non-specific systemic distribution and insufficient sensitivity for early lesion detection. Based on the above viewpoint, engineered Mn²⁺ nanoreactors demonstrate promising potential through diverse delivery platforms such as liposomes, metal-organic frameworks (MOFs), mesoporous materials, and self-propelled nanomotors. By leveraging acid/enzyme/redox-responsive mechanisms, these systems enable precise delivery and controlled release of Mn²⁺. Notably, the paramagnetic properties of Mn²⁺ support T₁-weighted MRI contrast, while integration with targeting ligands (e.g., RGD peptides, antibodies) facilitates tumor-specific localization. This innovative approach establishes a feedback-guided diagnostic-therapeutic paradigm for early-stage tumors through targeted imaging. We systematically examine recent advancements in engineered Mn²⁺ nanoreactors for cancer theranostics, with particular emphasis on molecular design strategies, stimulus-responsive mechanisms, and synergistic diagnostic-therapeutic effects. These insights provide valuable theoretical foundations for developing novel tumor management technologies with enhanced efficacy and reduced toxicity.