CuFeS(2) Nanoparticles Functionalized with a Thermoresponsive Polymer for Photothermia and Externally Controlled Drug Delivery

[Image: see text] CuFeS(2) chalcopyrite nanoparticles (NPs) can generate heat under exposure to near-infrared laser irradiation. Here, we develop a protocol to decorate the surface of CuFeS(2) NPs (13 nm) with a thermoresponsive (TR) polymer based on poly(ethylene glycol methacrylate) to combine heat-mediated drug delivery and photothermal heat damage. The resulting TR-CuFeS(2) NPs feature a small hydrodynamic size (∼75 nm), along with high colloidal stability and a TR transition temperature of 41 °C in physiological conditions. Remarkably, TR-CuFeS(2) NPs, when exposed to a laser beam (in the range of 0.5 and 1.5 W/cm(2)) at NP concentrations as low as 40–50 μg Cu/mL, exhibit a high heating performance with a rise in the solution temperature to hyperthermia therapeutic values (42–45 °C). Furthermore, TR-CuFeS(2) NPs worked as nanocarriers, being able to load an appreciable amount of doxorubicin (90 μg DOXO/mg Cu), a chemotherapeutic agent whose release could then be triggered by exposing the NPs to a laser beam (through which a hyperthermia temperature above 42 °C could be reached). In an in vitro study performed on U87 human glioblastoma cells, bare TR-CuFeS(2) NPs were proven to be nontoxic at a Cu concentration up to 40 μg/mL, while at the same low dose, the drug-loaded TR-CuFeS(2)-DOXO NPs displayed synergistic cytotoxic effects due to the combination of direct heat damage and DOXO chemotherapy, under photo-irradiation by a 808 nm laser (1.2 W/cm(2)). Finally, under a 808 nm laser, the TR-CuFeS(2) NPs generated a tunable amount of reactive oxygen species depending on the applied power density and NP concentration.