New Polylactic Acid Multifunctional Ultrasound ContrastAgent Based on Graphene Oxide as the Carrier of Targeted Factor andDrug Delivery

摘要

In recent years, the development of ultrasound contrast agents has encouraged their use as a drug system for diagnosis and therapy. In this paper, polylactic acid (PLA) composite microbubbles (FA/DOX/GO/DOX/PLA) were prepared with graphene oxide (GO) as a carrier of the targeted factor folic acid (FA) and doxorubicin (DOX) by the multiple emulsification–solvent evaporating process. Appearance, particle size, and zeta potential of PLA composite microbubbles were characterized by using a nanoparticle size analyzer and transmission electron microscopy. Breast cancer cells MCF-7 were used to evaluate the antitumor activity of PLA composite microbubbles in vitro by using the CCK-8 and acridine orange staining method. The ultrasonic imaging effect of PLA composite microbubbles was investigated in New Zealand white rabbits by the Doppler color ultrasound imaging system. With Kunming mice as the research model, the acute toxicity of PLA composite microbubbles was examined. The experimental results showed that the prepared PLA composite microbubbles presented a hollow and spherical shape with a particle size of 600nm or so and a zeta potential of −37.5 ± 10.0 mV. Theyhad a good effect of the enhancing imaging, and clear ultrasound imagingcan be obtained. PLA composite microbubbles showed a significant proliferationinhibition effect on breast cancer cells MCF-7 in a dose-dependentmanner. After PLA composite microbubbles were modified by FA, theywere good for targeting FA receptors on the surface of MCF-7 cells,which increased the inhibition rate of the tumor cells. LD50 of PLA composite microbubbles was 87.529 mg·kg^–1; the mice did not show the acute toxicity when the dose of compositemicrobubbles was lower than this value.