Fe₃O₄@Au@Cu₂₋<i>_x</i>S Heterostructures Designed for Tri‐Modal Therapy: Photo‐ Magnetic Hyperthermia and ⁶⁴Cu Radio‐Insertion

Abstract

Here, the synthesis and proof of exploitation of three-material inorganic heterostructures made of iron oxide-gold-copper sulfide (Fe₃ O₄ @Au@Cu_2-_x S) are reported. Starting with Fe₃ O₄ -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 Fe₃ O₄ surface. The saline stable trimers possess multi-functional properties: the Fe₃ O₄ 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 Fe₃ O₄ 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 Fe₃ O₄ @Au@Cu_2-_x S trimers suitable as carriers for ⁶⁴ Cu in internal radiotherapy (iRT) and traceable by positron emission tomography (PET).