Functionalized Biomimetic Magnetic Nanoparticles as Effective Nanocarriers for Targeted Chemotherapy

Novel MamC-mediated biomimetic magnetic nanoparticles (BMNPs) are proposed as valuable carriers for targeted chemotherapy because of the size (36 ± 12 nm) and of surface properties conferred by MamC coating. They are super-paramagnetic at room and body temperatures, have a large magnetic moment per particle, mediate hyperthermia, are cytocompatible, and, having a negative surface charge at physiological pH, can be efficiently coupled with DOXOrubicin (DOXO) and a monoclonal antibody (mAb) directed against the human Met/hepatocyte growth factor receptor (overexpressed in many cancers) displaying coupling stability, while releasing DOXO at acidic pH. This release can be enhanced by hyperthermia. The DOXO-mAb-BMNPs selectively recognize Met, bind efficiently to Met⁺ tumor cells, and discharge DOXO within their nuclei more efficiently than DOXO-BMNPs, exerting cytotoxicity. These data represent proof of concept for future in vivo experiments in which the controlled dual targeting (mAb-mediated and magnetic) approach and combined (chemotherapy and hyperthermia) therapy will be studied.