A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis

作者：Jiahao Gao, Ya Wang, Xianfu Meng, Xiaoshuang Wang, Fang Han, Hao Xing, Guanglei Lv, Li Zhang, Shiman Wu, Xingwu Jiang, Zhenwei Yao, Xiangming Fang, Jiawen Zhang, Wenbo Bu · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-52308-3 · 被引用次数：34 · 研究领域：Liver Disease Diagnosis and Treatment、Endoplasmic Reticulum Stress and Disease、Liver physiology and pathology

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients’ samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic. Molecular imaging holds promise for liver fibrosis grading but limited by a lack of effective biomarker. Here, the authors discover the grading potential of fibroblast activation protein alpha a...