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.