Triple-combination therapy assisted with ultrasound-active gold nanoparticles and ultrasound therapy against 3D cisplatin-resistant ovarian cancer model

Cancer chemotherapy suffers from drug resistance and side effects of the drugs. Combination therapies have been attracted attention to overcome these limitations of traditional cancer treatments. Recently, increasing in intracellular chemotherapeutic concentration in the presence of ultrasonic waves (US) has been shown in the preclinical stage. In addition, some recent studies have shown that nanoparticles increase the effectiveness of ultrasound therapy. In this study, the US-active property of gold nanocones (AuNCs) was utilized for combinational US and cisplatin (Cis) to overcome drug resistance. The effect of the triple combination therapy US + AuNCs + Cis with low-dose Cis on 2/3D models of cisplatin-resistant ovarian cancer cell line (A2780cis) were investigated. In the 2D cell culture, 60% of the A2780cis cell population was suppressed with triple combination therapy; and the long-term therapeutic efficacy of the US + AuNCs + Cis with the low-dose drug was demonstrated by suppressing 83% of colony formation. According to the results in the 3D cell model, 60% of the spheroid formation was suppressed by the triple combination therapy with low-dose Cis. These results not only demonstrate the success of the US + AuNCs + Cis triple combination therapy for its long-term therapeutic effect on resistant cancer cells but also verified that it might enable effective cancer therapy in vivo and clinical stages based on the 3D tumor models. In addition, enhanced anti-cancer activity was demonstrated at the low-dose Cis on drug-resistant cancer cells indicating the triple-combination therapy successfully overcame drug resistance and this is a promising strategy to reduce the side effects of chemotherapy. This work exhibits a novel US and AuNCs-mediated combination cancer therapy, which demonstrates the role of ultrasound-active AuNCs to combat drug resistance with low-dose chemotherapy.