Quantitative oncogene-mapping within malignant tumors through Multi-parameter MRI based on RNA-triggered nanoprobes

Genomic instability is the important foundation and feature of cancer; hence, the precise oncogene detection is crucial for early diagnosis and pathological analysis of tumors. However, the <i>in vivo</i> oncogene-imaging is confronted with great challenge, due to the extremely low copies of oncogene in cancer cells. Herein, we proposed a strategy of <i>T</i> ₁/<i>T</i> ₂ magnetic resonance imaging (MRI) based on magnetic resonance tuning (MRET) to analyze tumor-associated miRNA quantitatively. The superparamagnetic quencher Fe₃O₄ nanoparticles and the paramagnetic enhancer Gd-DTPA were integrated by the DNA linker. The AS1411 aptamer was embedded at the end of the DNA linker to effectively target nucleolins that are overexpressed in tumor cells. As hybridization with targeted miRNA, the Gd³⁺ labeled tumor-associated nucleotide sequence is released, enhancing <i>T</i> ₁ signals and enabling specific localization and quantification of the targeted miRNA. The MRET effect was verified <i>in vitro</i> through mixing with varying concentrations of miR-21. Enhanced <i>T</i> ₂ signals and activated <i>T</i> ₁ signals were visualized in 4T1 or CT26 subcutaneous tumor models <i>in vivo</i>. Ultimately, the quantitative relation between MRI signals and local miR-21 concentration was established <i>in vivo</i>. These results indicated the potential of nanoprobes for tumor-related genes diagnosis and quantification, further affirming the possibility of prompt and precise tumor diagnosis.