Fe3O4@Au@Cu2-xS Heterostructures Designed for Tri-Modal Therapy: Photo- Magnetic Hyperthermia and Cu-64 Radio-Insertion

Here, the synthesis and proof of exploitation of three-material inorganic heterostructures made of iron oxide-gold-copper sulfide (Fe3O4@Au@Cu2-xS) are reported. Starting with Fe3O4-Au dumbbell heterostructure as seeds, a third Cu2-xS domain is selectively grown on the Au domain. The as-synthesized trimers are transferred to water by a two-step ligand exchange procedure exploiting thiol-polyethylene glycol to coordinate Au and Cu2-xS surfaces and polycatechol-polyethylene glycol to bind the Fe3O4 surface. The saline stable trimers possess multi-functional properties: the Fe3O4 domain, of appropriate size and crystallinity, guarantees optimal heating losses in magnetic hyperthermia (MHT) under magnetic field conditions of clinical use. These trimers have indeed record values of specific adsorption rate among the inorganic-heterostructures so far reported. The presence of Au and Cu2-xS domains ensures a large adsorption which falls in the first near-infrared (NIR) biological window and is here exploited, under laser excitation at 808 nm, to produce photo-thermal heat alone or in combination with MHT obtained from the Fe3O4 domain. Finally, an intercalation protocol with radioactive Cu-64 ions is developed on the Cu2-xS domain, reaching high radiochemical yield and specific activity making the Fe3O4@Au@Cu2-xS trimers suitable as carriers for Cu-64 in internal radiotherapy (iRT) and traceable by positron emission tomography (PET).