A Synergistic Multiparametric MRI Strategy for FAPα-Targeted Tumor Fibrosis Based on NaGdF4@PEG-FAPI Nanoprobes

Abstract

Tumor-associated fibrosis, a key pathological feature of the tumor microenvironment (TME) is driven by cancer-associated fibroblasts (CAFs), promoting tumor progression and immune evasion, while fibroblast activation protein α (FAPα) overexpressed in over 90% of solid tumor stroma but absent in normal fibroblasts, serves as an ideal target for early tumor diagnosis via fibrotic lesion detection. Herein, we developed a FAPα-targeted nanoprobe NaGdF₄@PEG-FAPI for multiparametric MRI diagnosis of tumor Fibrosis. This nanoprobe was engineered for dual-mode T₁/T₂ MRI, enabling comprehensive tumor characterization. Extensive biosafety evaluations confirmed its excellent biocompatibility. In A549 subcutaneous tumor models, NaGdF₄@PEG-FAPI demonstrated superior performance. In Dynamic Contrast-Enhanced (DCE) Sequence, it provided high-resolution visualization of the tumor vasculature, significantly outperforming both Gd-DTPA and the non-targeted control (NaGdF₄@PEG-mal). Furthermore, the synergistic contrast bright enhancement in T₁-weighted imaging (T₁WI) and pronounced darkening in T₂*-weighted imaging (T₂*WI) convergently and reliably confirmed tumor localization. The FAPI-mediated active targeting endowed the nanoprobe with prolonged tumor retention and enhanced signal intensity. NaGdF₄@PEG-FAPI is highlighted as a robust and versatile platform in this study for multi-parameter, high-sensitivity tumor diagnosis.