Zwitterionic Manganese(III) Porphyrin as a Superoxide Dismutase Mimetic and MRI Contrast Agent

Manganese(III) porphyrins have been extensively investigated as both superoxide dismutase (SOD) mimics and magnetic resonance imaging contrast agents. However, a fundamental “charge contradiction” exists between their therapeutic and diagnostic applications: high SOD activity requires a cationic character, whereas effective MRI probes are typically anionic. To address this challenge, we designed zwitterionic Mn(III) porphyrins and evaluated them in vitro and in vivo for MRI contrast efficacy and SOD-like activity in an acute kidney injury (AKI) model. These complexes showed a relaxivity of 8–9 mM–1s–1 (1.41 T) and biocompatibility comparable to anionic analogues while retaining SOD-like activity similar to cationic ones. Cytotoxicity and uptake studies revealed balanced charge mitigation and modulated internalization. Zwitterionic MnT-4-PyP-COOH demonstrated pronounced MRI signal enhancement, excellent biocompatibility, and potent antioxidant activity in a lipopolysaccharide-induced murine model of AKI. This work offers a rational design strategy for dual-functional agents that enable combined MR imaging and antioxidant therapy.