Multifunctional and Redox-Responsive Self-Assembled Magnetic Nanovectors for Protein Delivery and Dual-Modal Imaging

Nanoparticle (NP) based model carriers present an emerging strategy for protein delivery. However, constructing a multifunctional nanocarrier with high loading capacity, diagnostic imaging capacity, and controlled release capability is a tremendous challenge for protein delivery systems. Thus, we herein report on the fabrication of redox-responsive magnetic nanovectors (termed RMNs) through self- assembly of Fe₃O₄ NPs and redox-responsive polymer ligands, which could effectively transport protein and trigger intracellular protein release. These RMNs also exhibited low toxicity, high stability, biocompatibility, and T₂-weighted contrast-enhancement properties. In addition, they presented a quantized positively charged surface that had the capacity to load cyanine 5.5 (Cy5.5) labeled human serum albumin (HSA) with high loading efficiency (∼84%) via electrostatic interactions and which favored cellular uptake. Notably, studies of the in vitro protein release showed that HSA-Cy5.5-loaded RMNs (RMNs-HSA-Cy5.5) presented minimal cumulative release behavior under physiological conditions but release was rapidly enhanced under high glutathione concentration conditions. Confocal microscopy further revealed that protein was delivered and localized at the perinuclear region of tumor cells. Moreover, the in vivo imaging results confirmed that RMNs-HSA-Cy5.5 could serve as a dual-modal probe for simultaneous near-infrared fluorescence (NIRF) imaging and magnetic resonance (MR) imaging, which can be used for breast cancer diagnosis, and verified higher tumor accumulation of transported protein in a living body. Overall, we believe that these multifunctional RMNs exhibit great promise for protein delivery, cancer diagnosis and therapy, and multimodal imaging, as well as clinical applications.