Dual-Mode Tumor Diagnosis and Guided Precise Photodynamic Therapy Based on MicroRNA Fluorescence Signal Amplification and Magnetic Resonance Imaging.

Abstract

Accurate and early tumor diagnosis is critical for effective cancer treatment, yet current diagnostic modalities often face limitations. Fluorescence imaging (FLI) and magnetic resonance imaging (MRI) both offer substantial potential for cancer diagnosis. However, FLI suffers from poor tissue penetration, while MRI lacks molecular specificity. To address these limitations, we proposed a dual-modal diagnostic strategy by combining FLI and MRI for precise photodynamic therapy (PDT) of tumors. A degradable tumor microenvironment (TME)-responsive nanoplatform, i.e., UCNPs-MB@MnO₂-H1/H2 (UBMD), was developed. Intracellular overexpression of miRNA-21 triggers an in situ hybridization chain reaction between H1-TAMRA and H2-FAM, which significantly amplifies fluorescence resonance energy transfer and enables FLI of miRNA-21 in living cancer cells. On the other hand, UBMD activates MRI in the TME to remarkably amplify tumor MRI signals and to effectively compensate for the shortcoming of weak penetration of FLI in deep tissues. UBMD exhibits an NIR-activated PDT capability to enable tumor-specific in situ diagnostics and imaging. In vivo miRNA-21 FLI and MR imaging in living mice actively guide precise and efficient PDT of tumors.