Development of Hollow Gold Nanoparticles for Photothermal Therapy and Their Cytotoxic Effect on a Glioma Cell Line When Combined with Copper Diethyldithiocarbamate

Abstract

Gold-based nanoparticles hold promise as functional nanomedicines, including in combination with a photothermal effect for cancer therapy in conjunction with chemotherapy. Here, we synthesized hollow gold nanoparticles (HGNPs) exhibiting efficient light absorption in the near-IR (NIR) region. Several synthesis conditions were explored and provided monodisperse HGNPs approximately 95–135nm in diameter with a light absorbance range of approximately 600–720nm. The HGNPs were hollow and the surface had protruding structures when prepared using high concentrations of HAuCl4. The simultaneous nucleation of a sacrificial AgCl template and Au nanoparticles may affect the resulting HGNPs. Diethyldithiocarbamate (DDTC) is metabolized from disulfiram and is a repurposed drug currently attracting attention. The chelation of DDTC with copper ion (DDTC-Cu) has been investigated for treating glioma, and here we confirmed the cytotoxic effect of DDTC-Cu towards rat C6 glioma cells in vitro. HGNPs alone were biocompatible and showed little cytotoxicity, whereas a mixture of DDTC-Cu and HGNPs was cytotoxic in a dose dependent manner. The temperature of HGNPs was increased by NIR-laser irradiation. The photothermal effect on HGNPs under NIR-laser irradiation resulted in cytotoxicity towards C6 cells and was dependent on the irradiation time. Photothermal therapy by HGNPs combined and DDTC-Cu was highly effective, suggesting that this combination approach hold promise as a future glioma therapy.