Enhanced tumor-targeting ability of transferrin-functionalized magnetic nanoparticles by in vivo AMF stimulation

The protein corona formed on the surface of ligand-functionalized nanoparticles has been associated with the loss of targeting capability of the nanoparticles in vivo. Here, we developed a remote magnetothermal stimulation approach to regulate the in vivo active-targeting capability of transferrin (Tf)-functionalized magnetic nano- particles (SPIO-Tf). This technique harnesses the heat dissipation by the magnetic nanoparticles in response to alternating magnetic fields to re-expose buried Tf on the nanoparticle surface, thereby restoring its binding function. SPIO-Tf with different grafting densities were prepared and in vitro experiments reveal that AMF stimulation of SPIO-Tf significantly improved its targeting ability to A549 cells in serum-rich environments. In vivo experiments also exhibit a 2.68-fold greater accumulation of magnetothermal-stimulated SPIO-Tf in solid tumors. Moreover, our approach is applicable to various SPIO-Tf formulations with different PEG molecular weights, and antibodies-conjugated SPIO. Overall, this study establishes a versatile, safe and potent strategy to tackle the negative impact of protein corona on the targeting ability of ligand-decorated magnetic nanoparticles in vivo, with promising implications for enhancing the effectiveness of diagnostic and therapeutic interventions across a range of diseases.