Coordination-Responsive Longitudinal Relaxation Tuning as a Versatile MRI Sensing Protocol for Malignancy Targets

Abstract

Biomarkers (e.g., acidity, H2O2, hypoxia, and specific molecules) as one primary component of tumor microenvironments are closely associated with occurrence, invasion, and metastasis of malignancy, thus can act as biological targets. However, their monitoring remains a challenging task. Herein, a coordination-dependent longitudinal relaxation tuning (CLRT) that occurs between a Mn2+ “donor” and a Mn2+ “acceptor” is established to enable biological target sensing. Relying on the differences of coordination ability and spatial structure between donors and acceptors, the biological targets as Mn2+ acceptor can take Mn2+ away from the donors (i.e., modified ligands) in nanoscale probes, which consequently varies T1-weighted (T1W) magnetic resonance imaging (MRI) signal. The coordination ability and spatial structure of the modified Mn2+ “donor” and the pore diameter of donor carrier are demonstrated to determine the feasibility, specificity, and generality of CLRT. With CLRT, this MRI-based ruler is demonstrated for the successful specific detection of biological targets (i.e., hyaluronic acid and glutathione) of malignancy, and its potential in quantitative measurement of hyaluronic acid is further demonstrated. CLRT can serve as a novel and general sensing principle to augment the exploration of a wide range of biological systems.