Liposomal nanoprobes actuated by engineered water channels for sensitive detection of molecular targets by MRI

Monitoring biochemical processes requires tools to detect specific molecular species in vivo. Although responsive probes detectable by MRI enable this, conventional MRI contrast agents often lack sufficient sensitivity. Here we circumvent this limitation using nanoscale probes constructed from pore-forming peptides incorporated into paramagnetic liposomes. In our design, target molecules control MRI contrast by regulating water access to liposome-encapsulated gadolinium chelators. The large ratio of gadolinium complexes to pores provides a sensitivity gain by over an order of magnitude compared with small-molecule MRI sensors. We demonstrate the probe architecture using biotin as a model analyte and gramicidin A as the basis for responsive pores. We then validate the biotin-sensitive liposomal probes in vitro and in rat brain, and we show that minimally invasive delivery to multiple tissue types is feasible. Furthermore, we identify pore sequences that provide greater MRI contrast effects than native gramicidin and we demonstrate that further channel modifications permit detection of different target molecules. This work thus introduces a potent and engineerable technology for molecular imaging in living systems.