Ultrasound-controlled DOX-SiO2 nanocomposites enhance the antitumour efficacy and attenuate the toxicity of doxorubicin

Abstract

The toxicity of doxorubicin (DOX), especially in terms of cardiotoxicity, has been a common problem in its clinical use. In our studies, we synthesized and characterized DOX-SiO₂ nanocomposites. In the in vitro experiments, DOX-SiO₂ nanocomposites could more effectively induce apoptosis, inhibit colony formation, and inhibit the proliferation of the cancer cell line HeLa compared with free DOX. Furthermore, ultrasound could dramatically enhance these abilities of DOX-SiO₂ nanocomposites. The in vivo studies showed that DOX-SiO₂ nanocomposites increased the concentration of DOX in the tumour region and decreased the concentration of DOX in normal tissues. Additionally, DOX-SiO₂ nanocomposites under ultrasound could inhibit growth and increase the apoptosis of xenograft tumour cells more effectively than DOX-SiO₂ nanocomposites alone. Meanwhile, the cardiotoxicity of DOX was significantly reduced by DOX-SiO₂ nanocomposites. The difference was more obvious in DOX-SiO₂ nanocomposites under ultrasound. Moreover, prolonging the ultrasound time augments the antitumour efficacy and attenuates the toxicity of DOX-SiO₂ nanocomposites. In summary, we concluded that DOX-SiO₂ nanocomposites under ultrasound decrease DOX-induced toxicity in normal tissues and increase the antitumour effect of DOX by targeted delivery and controllable release, which shows the great potential of DOX-SiO₂ nanocomposites for the delivery of DOX in the clinic.