A new PLA–Tween composited drug-carrying C60–Fe(3)O(4) multifunctional ultrasound contrast agent based on three kinds of lesions

A PLA–Tween composited drug-carrying C60–Fe(3)O(4) microbubble was designed and prepared. Using Fe(3)O(4) as a targeting factor and C60 as a drug carrier, warfarin (WF), netimixin (NET) and doxorubicin (DOX) respectively were loaded on a C60–Fe(3)O(4) complex through π–π conjugate effect, and C60–Fe(3)O(4)–WF, C60–Fe(3)O(4)–NET and C60–Fe(3)O(4)–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–Fe(3)O(4)–DOX microbubbles, PLA–Tween composited C60–Fe(3)O(4)–NET microbubbles and PLA–Tween composited C60–Fe(3)O(4)–WF microbubbles were obtained, respectively. The average particle size of PLA–Tween composited drug-carrying C60–Fe(3)O(4) 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–Fe(3)O(4) microbubbles were 5.58%, 8.15% and 3.37%, respectively. PLA–Tween composited C60–Fe(3)O(4)–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–Fe(3)O(4)–NET microbubbles had a inhibitory effect on the growth of Staphylococcus aureus and Escherichia coli, and the inhibitory effect on Escherichia coli was better. PLA–Tween composited C60–Fe(3)O(4)–WF microbubbles could inhibit the formation of thrombus, and PT, TT and APTT were significantly prolonged. PLA–Tween composited C60–Fe(3)O(4) 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.