Ultrasound-exposed folate receptor-targeted doxorubicin-loaded gold nanoparticles decreased KB-hFR cell viability by up to 70% and increased necrotic cells by up to 45% compared to untreated cells.
Does ultrasound exposure of doxorubicin-loaded gold nanoparticles improve cancer cell killing in KB-hFR cells?
Ultrasound-responsive doxorubicin-loaded gold nanoparticles demonstrate synergistic anticancer activity through targeted drug release and enhanced ROS production in vitro.
Both doxorubicin and gold nanoparticles (GNPs) exhibit sonosensitising properties, significantly increasing the production of cytotoxic reactive oxygen species (ROS) when exposed to ultrasound (US). Ultrasound-responsive, targeted GNPs decorated with a pH-releasable doxorubicin prodrug (FDGNPs) have been developed to exploit this synergistic effect, enabling highly selective and effective anticancer activity. The GNPs were produced using the Turkevich method and functionalised with folate-PEG 3.5 kDa -SH as the targeting agent (FGNPs). These were then decorated with doxorubicin derivatised with lipoic acid via a pH-sensitive linker and stabilised with a mPEG 2 kDa -SH coating. The FDGNPs’ cell targeting, uptake and anticancer effects were evaluated in an epidermoid carcinoma cell line expressing a high level of folate receptor (KB-hFR), which was cultured as monolayers and three-dimensional spheroids. The anticancer effects of the US-exposed FDGNPs were evaluated in terms of cell viability, ROS production and cell death. FDGNPs selectively associated to KB cells in a folate-dependent manner. Ultrasound-exposed FDGNPs resulted in a significant decrease in KB-hFR cell viability of up to 70 %, increased ROS of up to 50 %, and increased necrotic cells of up to 45 %, compared to untreated cells. Furthermore, switching from a custom-built US device to a standardised US scanning device confirmed that US exposure effectively elicits the anticancer activity of FDGNPs in KB-hFR spheroids, resulting in a 45 % decrease in cell viability. GNPs have been engineered to provide active targeting and controlled drug release while exploiting their sonosensitising properties; therefore, this platform shows promise in improving the selectivity and efficacy of cancer therapy. • Tuning of folate receptor-targeted doxorubicin-loaded gold nanoparticles (FDGNPs). • FDGNPs release doxorubicin under acidic pH and ultrasound (US) exposure. • US-exposed FDGNPs generate a high level of cytotoxic reactive oxygen species. • US exposure of FDGNPs results in the selective killing of cancer cells. • An US scan is used to induce FDGNPs-mediated cancer cell death in cancer spheroids.
Foglietta et al. (Fri,) conducted a other in Epidermoid carcinoma. Ultrasound-exposed folate receptor-targeted doxorubicin-loaded gold nanoparticles (FDGNPs) vs. Untreated cells was evaluated on Cell viability, ROS production and cell death. Ultrasound-exposed folate receptor-targeted doxorubicin-loaded gold nanoparticles decreased KB-hFR cell viability by up to 70% and increased necrotic cells by up to 45% compared to untreated cells.