Transferrin-Targeted Nanoplatform for MRI-Guided Visualization and Potent Suppression of Tumors and Pulmonary Metastatic Lesion

Abstract

While targeted theranostics for cancer remains a pivotal research frontier, conventional ligand conjugation strategies exhibit persistent limitations in off-target accumulation and suboptimal tumor specificity, ultimately failing to achieve reliable detection of early-stage lesions or metastatic nodule while demonstrating insufficient therapeutic payload delivery. In this study, the manganese sulfide (MnS) nanoplatform was synthesized using transferrin (Tf) with tumor-targeting properties as carrier by a simple fabrication method. Notably, compared to clinically prevalent Gd-based contrast agents, Tf-MnS exhibited superior T1-weighted magnetic resonance imaging (MRI) contrast performance, with the longitudinal relaxation (r1) reaching 7.5253 mM-1 •s-1 which was significantly higher than 3.2915 mM-1 •s-1 of Gd-DTPA, and in the MRI of subcutaneous tumors and lung metastatic lesion in mice, the maximum relative signal-to-noise ratios reached 46.33% and 40.33% respectively. Remarkably, upon reaching the acidic tumor microenvironment, Tf-MnS disintegrated to release Mn2+ ions and hydrogen sulfide (H2S). The Mn2+ ions participated in Fenton-like reactions to produce cytotoxic hydroxyl radicals, while H2S concurrently inhibited catalase enzyme activity, thereby alleviating the insufficiency of hydrogen peroxide substrate and amplifying the therapeutic outcome. This synergistic mechanism endowed Tf-MnS with self-enhanced anti-tumor effect, inhibiting both lung metastatic lesion and subcutaneous tumors in mice of the Tf-MnS group, with a tumor inhibition rate of 54.26%. Collectively, this work proposes an innovative strategy for integrating accurate diagnosis and self-augmented therapy of tumors and lung metastatic lesion into a unified nanoplatform, offering a promising methodology for precision oncology.