A switchable magnetic resonance imaging nanoplatform for <i>in situ</i> microRNA imaging

Aberrant microRNA (miRNA) expression is associated with various types of carcinogenesis, making miRNA a promising candidate for diagnostic and therapeutic biomarkers. However, <i>in situ</i> miRNA diagnostics remains a significant challenge owing to the various biological barriers. Herein, we report a novel miRNA imaging probe consisting of PEG-polylysine-PNIPAM polymer matrix-modified small Fe₃O₄ (PAA-Fe₃O₄-DNA@PPP) nanoparticles with an improved circulatory half-life, efficient tissue permeability, and enhanced tumor accumulation, for <i>in situ</i> miRNA magnetic resonance imaging (MRI). In this strategy, we employed large size PAA-Fe₃O₄-DNA@PPP to improve circulatory time and utilized PEG-polylysine-PNIPAM as a GSH-responsive moiety to dissociate PAA-Fe₃O₄-DNA@PPP and release small size PAA-Fe₃O₄-DNA for enhanced tumor permeability. Specifically, the target miRNA acts as a cross-linker for PAA-Fe₃O₄-DNA, forming larger assemblies that not only amplify the MRI signal for detection but also enhance retention for prolonged observation. Both the <i>in vitro</i> and <i>in vivo</i> results validate that the imaging probe exhibits an enhanced MRI signal with 3.69-fold amplification for tumor interior miRNA detection, allowing the dynamic changes in miRNA to be monitored by the probe. Given its long circulation, efficient penetration, and enhanced tumor accumulation, the PAA-Fe₃O₄-DNA@PPP probe holds great promise for <i>in situ</i> miRNA imaging and spatial genomics analysis <i>in situ</i>.