A new PLA-Tween composited drug-carrying C60-FeO multifunctional ultrasound contrast agent based on three kinds of lesions.

A PLA-Tween composited drug-carrying C60-FeO microbubble was designed and prepared. Using FeO as a targeting factor and C60 as a drug carrier, warfarin (WF), netimixin (NET) and doxorubicin (DOX) respectively were loaded on a C60-FeO complex through π-π conjugate effect, and C60-FeO-WF, C60-FeO-NET and C60-FeO-DOX targeted drug-loading complexes were obtained. The three drug-loading complexes were respectively combined into PLA and Tween membrane material, PLA-Tween composited C60-FeO-DOX microbubbles, PLA-Tween composited C60-FeO-NET microbubbles and PLA-Tween composited C60-FeO-WF microbubbles were obtained, respectively. The average particle size of PLA-Tween composited drug-carrying C60-FeO microbubbles was 446.4 nm, the microbubble size was uniform, and the Zeta potential was -40.5 mV which showed a good stability. The loading rates of DOX, NET and WF in PLA-Tween composited drug-carrying C60-FeO microbubbles were 5.58%, 8.15% and 3.37%, respectively. PLA-Tween composited C60-FeO-DOX microbubbles could inhibit the breast cancer MDA-MB-231 cells and normal mouse fibroblast 3T3 cells, the inhibition rates were respectively 53.4% and 18.6%, which significantly reduced the toxicity of free DOX drug on the normal cells (62.2%). PLA-Tween composited C60-FeO-NET microbubbles had a inhibitory effect on the growth of and , and the inhibitory effect on was better. PLA-Tween composited C60-FeO-WF microbubbles could inhibit the formation of thrombus, and PT, TT and APTT were significantly prolonged. PLA-Tween composited C60-FeO microbubbles had a developing effect on the kidney, bladder and abdominal aorta of rabbit. Under the action of external magnetic field, the ultrasonic imaging effect of composite microbubbles was significantly enhanced.