Programmable MRI contrast switching for spatiotemporal mapping of thrombus maturation via enzyme-directed nanoprobe reconfiguration

Abstract

Spatiotemporal mapping of thrombus remodeling remains a major unmet challenge due to the lack of diagnostic tools capable of dynamically converting local biochemical activity into quantitative imaging signals. Current clinical methods lack sensitivity and specificity for accurate thrombus staging. Here, we present a programmable MRI nanoplatform enabling enzyme-gated dual-mode contrast switching for dynamic thrombus profiling and guided thrombolysis. The nanoprobe achieves broad-spectrum thrombus targeting by recognizing two complementary biomarkers uniquely expressed at distinct thrombus maturation stages, and integrates gelatin-guided structural reconfiguration with magnetic nanoparticle clustering to modulate MRI contrast. Gelatin modulates the nanoprobe structure, restricting water proton accessibility and promoting internal densification, thereby synchronously suppressing T1-weighted signals and amplifying T2-weighted contrast. Upon activation by thrombus-associated MMP-2/9, the nanoprobe disassembles, reversing its nano-architecture and signal behavior. This smart signal transformation quantitatively correlates with MMP activity, thrombus age, and collagen content, generating stage-dependent T1/T2 ratios. The nanoprobe also enables enzyme-triggered fibrinolytic release, achieving site-specific thrombolysis with minimal hemorrhagic risk. This materials-based strategy translates dynamic microenvironmental remodeling into high-resolution MRI outputs, establishing a programmable framework for precision imaging and therapy. These programmable imaging outputs support data-driven diagnostics, enable clinical treatment stratification, and offer a standardized reference for modeling enzyme-rich pathological environments.

Graphical Abstract