Effect of drug-loaded microbubbles combined with ultrasound on the apoptosis of cancer cells.

The aim of the present study was to investigate whether drug-loaded microbubbles combined with ultrasound promotes the apoptosis of cancer cells by regulating Bcl-2 and Bax expression. Adriamycin-loaded PLGA nanoparticles (ADM-NP) were fabricated using a modified emulsification process. Lipid microbubbles (NH2 -MB) were prepared by mechanical vibration. The carboxyl groups of ADM-NP and NH2 -MB underwent a condensation reaction after 48 h and adriamycin-loaded PLGA nanoparticles microbubble complexes (ADM-NMC) were obtained. High performance liquid chromatography demonstrated that the entrapment efficiency and drug loading of ADM-NMC were 85.32±5.41% and 7.91±0.27%, respectively. The VX2 liver cancer model was established in 30 New Zealand rabbits, which were divided into 3 groups: A Control group received 5 ml saline, an ADM-NP group that received 5 ml ADM-NP and an ADM-NMC group that received 5 ml ADM-NMC. Rabbits in the ADM-NP and ADM-NMC groups underwent irradiation 120 sec with low frequency ultrasound for 120 sec following injection. The echogenicity of tumors markedly increased following ADM-NP and ADM-NMC treatment. Staining with hematoxylin and eosin demonstrated that the tumor shape became more normal in the ADM-NP and ADM-NMC groups compared with the control group. The expression of Bax was increased and the expression of Bcl-2 was decreased following treatment with ADM-NP and ADM-NMC. Cancer cell apoptosis was significantly increased following treatment with ADM-NP and ADM-NMC. Our study demonstrated that drug-loaded microbubbles combined with ultrasound may enhance the efficiency of tumor inhibition. This may be due to the promotion of cancer cell apoptosis via regulation of Bax and Bcl-2 expression.