Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment

SIMPLE SUMMARY: Polyphenols are present in a broad variety of plants, and they are known to possess anti-inflammation and anticancer properties. We used extracts from Laurus nobilis to synthetize gold nanoparticles (Au NPs), on which polyphenols were absorbed to form a stable shell (Au NPs@polyphenols). Then, the macrophage inflammation response was assessed, with the aim of using the Au NPs@polyphenols as synergistic tools in the thermal treatment of cancer cell models. We showed that the thermal conductivity enhancement, induced by Au during thermal treatment, increased the anticancer effects of polyphenols. After demonstrating the effectiveness of this system in in vitro cancer cell models, the future challenge will be the in vivo application of Au NPs@polyphenols. ABSTRACT: Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment.