Homotypic-Targeted Mineralized Tumor Cell Probes for Ultrasensitive MRI Diagnosis of Early-Stage Malignancies

The effectiveness of clinically used magnetic resonance imaging (MRI) contrast agents (CAs) in tumor diagnosis is limited due to their low selectivity and sensitivity. To address this, we propose inactivated cell-based contrast agents (Mn-CCs) by constructing a mineralized tumor cell. Preserving proteins and structures on the cell membrane, Mn-CCs exhibit advantages, including homotypic targeting capabilities, tumor microenvironment (TME)-activated MRI signals, and ultrahigh relaxation rates. Glioma and pancreatic tumor cells were used as model templates to produce Mn-UCs and Mn-SCs. Under TME conditions, the longitudinal relaxation rates of Mn-UCs and Mn-SCs increased to 13.27 and 5.48 mM-1s-1, respectively. In vivo results demonstrated that Mn-UCs showed a superior MRI contrast enhancement in glioma compared to clinically used Gd-DOTA. Furthermore, Mn-SCs specifically enhanced MRI contrast in pancreatic tumors as small as 5.67 ± 1.16 mm3 and enabled clear differentiation between tumor stages. The biosafety, sensitivity, and specificity of Mn-CCs suggest a novel approach for designing biomimetic MRI contrast agents, offering new opportunities for more precise diagnosis of early-stage tumors.