Fe 3 O 4 @Au@Cu 2- x S Heterostructures Designed for Tri-Modal Therapy: Photo- Magnetic Hyperthermia and 64 Cu Radio-Insertion.

Here, the synthesis and proof of exploitation of three-material inorganic heterostructures made of iron oxide-gold-copper sulfide (Fe 3 O 4 @Au@Cu 2- x S) are reported. Starting with Fe 3 O 4 -Au dumbbell heterostructure as seeds, a third Cu 2- x S 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 Cu 2- x S surfaces and polycatechol-polyethylene glycol to bind the Fe 3 O 4 surface. The saline stable trimers possess multi-functional properties: the Fe 3 O 4 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 Cu 2- x S 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 Fe 3 O 4 domain. Finally, an intercalation protocol with radioactive 64 Cu ions is developed on the Cu 2- x S domain, reaching high radiochemical yield and specific activity making the Fe 3 O 4 @Au@Cu 2- x S trimers suitable as carriers for 64 Cu in internal radiotherapy (iRT) and traceable by positron emission tomography (PET).