Dual-ratiometric magnetic resonance tunable nanoprobe with acidic-microenvironment-responsive property to enhance the visualization of early tumor pathological changes

The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging (MRI), with the advantage of significantly improved specificity and good biocompatibility. However, the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor progression. Here, we report on a dual-ratiometric magnetic resonance tunable (DMRT) nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles, complexed to a pH responsive biocompatible polymer. This dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization, providing exceptional quantitative pathophysiological information in vitro and in vivo. When used in combination with dual-contrast enhancement triple subtraction imaging technique (DETSI), this smart nanoprobe guarantees the diagnosis of early-stage diseases. We envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging, as well as microenvironment visualization and disease progression monitoring.