Manganese-Loaded pH-Responsive DNA Hydrogels Enable Tg-Guided Thyroid Tumor Targeted Magnetic Resonance Imaging

The diagnosis of metastatic and recurrent occult thyroid cancer presents a significant challenge. This study introduces a DNA-Mn hydrogel (M-TDH) that specifically targets thyroglobulin (Tg). This nanogel is loaded with paramagnetic Mn²⁺ for facilitating magnetic resonance (MR) imaging. As a cofactor of DNA polymerase, Mn²⁺ promotes the extension of long-strand DNA and forms Mn₂PPi nuclei with PPi^4- in the system. The synthesis of M-TDH is achieved through Mn₂PPi nucleation and growth with long-strand DNA acting as the structural framework. The X-scaffold functions as a junction point, thereby enhancing structural stability. The Tg aptamer sequence is incorporated into M-TDH, ensuring specific targeting of thyroid cancer cells. Furthermore, M-TDH demonstrates an extended residence time at the thyroid tumor site, thus increasing the duration of enhanced MR imaging. Overall, this study introduces an aptamer-based, thyroid tumor-targeted DNA nanogel for MR imaging diagnostic applications, with the potential to advance a multifunctional magnetic nanosystem toward clinical application.