A Targeted Multi-Crystalline Manganese Oxide as a Tumor-Selective Nano-Sized MRI Contrast Agent for Early and Accurate Diagnosis of Tumors

作者：Gongxin Yang, Jikai Xia, Xiaoqing Dai, Hongbo Zhao, Weiqing Gao, Weilong Ding, Xiaofeng Tao, Ling Zhu · 发表于：International Journal of Nanomedicine · 年份：2024 · DOI：10.2147/ijn.s444061 · 被引用次数：6 · 研究领域：Nanoparticle-Based Drug Delivery、Lanthanide and Transition Metal Complexes、Graphene and Nanomaterials Applications

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 Mn 2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn 2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T 1 -weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T 1 -weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T 1 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