Transferrin-Targeted Nanoarchitectonics with Efficient Metastasis Inhibition Enabling Tumor T₁-T₂ Dual-Mode Magnetic Resonance Contrast Enhancement.

Abstract

The development of T₁-T₂ dual-mode contrast agents is expected to improve cancer diagnostic capabilities in response to the limitation of traditional single-mode magnetic resonance imaging (MRI) contrast agents. In this study, a pH-responsive dual-mode MRI nanoprobe, Fe₃O₄@MnS-transferrin (FMT), is prepared with the objective of augmenting tumor visualization and chemodynamic therapy (CDT). FMT achieved precise tumor targeting by binding to transferrin receptors on cancer cells via the transferrin molecules on their surface. FMT underwent pH-responsive decomposition in the acidic tumor microenvironment, releasing Fe₃O₄ and Mn²⁺. This decomposition increased the spatial separation between Fe₃O₄ and Mn²⁺, attenuating the mutual magnetic shielding effect and activating dual-mode MRI function. Moreover, FMT released Mn²⁺ and hydrogen sulfide (H₂S). Mn²⁺ triggered a Fenton-like reaction, generating reactive oxygen species that induced cytotoxicity through CDT. Concurrently, H₂S inhibited catalase activity, providing additional substrates for the Fenton-like reaction, thereby amplifying CDT in a cascading manner. This synergistic mechanism amplified the cytotoxicity of CDT, enhancing the efficacy of tumor treatment and metastasis inhibition. Therefore, FMT demonstrated significant promise for enhancing both the precision of tumor imaging and the efficacy of treatment.