Carbonized paramagnetic complexes of Mn (II) as contrast agents for precise magnetic resonance imaging of sub-millimeter-sized orthotopic tumors

• Published in: Nature communications Vol. 13; no. 1; pp. 1938 - 16
• Main Authors: Qin, Ruixue, Li, Shi, Qiu, Yuwei, Feng, Yushuo, Liu, Yaqing, Ding, Dandan, Xu, Lihua, Ma, Xiaoqian, Sun, Wenjing, Chen, Hongmin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.04.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 59; 59/57; 631/67/2321; 692/700/1421/1628; 692/700/1421/2160; Animals; Biocompatibility; Biomedical materials; Blood-brain barrier; Brain cancer; Brain tumors; Contrast agents; Contrast Media; Gadolinium; Gadopentetate dimeglumine; Glioma; Glioma cells; Humanities and Social Sciences; In vivo methods and tests; Ions; Liver - pathology; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Manganese; Medical imaging; Mice; multidisciplinary; Nanoparticles; Neuroimaging; Nodules; Pollutant deposition; Resonance; Science; Science (multidisciplinary); Sensitivity; Toxicity; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29586-w

Paramagnetic complexes containing gadolinium ions have been widely used for magnetic resonance imaging (MRI) in clinic. However, these paramagnetic complexes pose some safety concerns. There is still a demand for the development of stable MRI contrast agents that exhibit higher sensitivity and superior functionality to existing contrast agents. Here, we develop carbonized paramagnetic complexes of manganese (II) (Mn@CCs) to encapsulate Mn 2+ in sealed carbonized shells with superhigh r 1 relaxivity. Compared to the most common clinical contrast agent Magnevist, investigations in vivo demonstrate that the Mn@CCs cross the intact blood-brain barrier of normal health mice with minor metal deposition; preferentially target the glioma tissues distribute homogeneously with high penetration in an intracranial mouse model; delineate clear tumor margins in MRIs of ultrasmall single-nodule brain tumors, and multi-nodular liver tumors. The sensitivity, accuracy and low toxicity offer by Mn@CCs provides new opportunities for early molecular diagnostics and imaging-guided biomedical applications. Improving the imaging of cancer may enhance the treatment of patients, Here, the authors develop a Mn(II) based nanoparticle contrast agent for MRI imaging and show that the nanoparticles can cross the brain barrier and image glioma cells.