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

摘要

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.