Sialic Acid-Functionalized Iron-Based Metal–Organic Framework Nanoprobe for Tumor-Targeted Near-Infrared Fluorescence/Magnetic Resonance Imaging of Cervical Cancer

Abstract Accurate localization and delineation of cervical cancer lesions are essential for precise surgical planning. However, conventional magnetic resonance imaging (MRI) often provides insufficient molecular specificity for tumor delineation, whereas near-infrared fluorescence (NIRF) imaging is restricted by shallow tissue penetration. Herein, we developed a sialic acid (N-Acetylneuraminic acid, Neu5Ac)-functionalized nanoscale iron-based metal–organic framework (MOF) nanoprobe, NH2-MIL-101(Fe)/Neu5Ac/Cy7, for tumor-targeted NIRF/MR dual-modal imaging of cervical cancer. The nanoscale Fe-MOF framework provides intrinsic T2-weighted MR contrast and serves as a functional scaffold for PEG/Neu5Ac surface modification and Cy7 loading. In SiHa cells, the Neu5Ac-functionalized nanoprobe exhibited approximately 2.1-fold and 3.9-fold higher intracellular fluorescence than the non-Neu5Ac-modified counterpart at 8 and 12 h, respectively. Time-dependent in vivo NIRF imaging further identified 8 h postinjection as a suitable imaging time point. In SiHa tumor-bearing mice, NH2-MIL-101(Fe)/Neu5Ac/Cy7 showed enhanced tumor-associated accumulation compared with control probes, as evidenced by pronounced T2-weighted MR signal attenuation and a 4.36-fold higher ex vivo tumor fluorescence intensity than the non-Neu5Ac-modified counterpart. Collectively, this nanoscale dual-modal imaging platform combines MRI-based deep-tissue localization with NIRF imaging sensitivity, offering a promising strategy for cervical cancer lesion visualization and tumor-region delineation.