Introduction: Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy.
Methods: Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO).
Results: The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn²⁺ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn²⁺ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T₁-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T₁-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T₁ contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells.
Conclusion: Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.

Keywords: multi-crystalline manganese oxide, MRI contrast agent, tumor targeting, tumor selectivity, accurate diagnosis