Therapeutic ultrasonic microbubbles carrying paclitaxel and LyP-1 peptide: preparation, characterization and application to ultrasound-assisted chemotherapy in breast cancer cells.

The aim of this work was to develop a novel targeted drug-loaded microbubble (MB) and to investigate its chemotherapy effect in vitro. Paclitaxel (PTX)-loaded lipid MBs were prepared by a mechanical vibration technique. The LyP-1, a breast tumor homing peptide, was coated onto the surface of PTX-loaded MBs through biotin-avidin linkage. The resulting targeted drug-loaded MBs were characterized and applied to ultrasound-assisted chemotherapy in breast cancer cells. Our results showed the ultrasonic MBs were able to achieve 43%-63% of drug encapsulation efficiency, depending on drug loading amount. The binding affinity assay indicated the attachment of targeted MBs to human MDA-MB-231 breast cancer cells was highly efficient and stable even with ultrasonic irradiation on. The cellular uptake efficiency of payload in targeted MBs was 3.71-, 4.95-, 7.43- and 7.66-fold higher than that of non-targeted MBs at the applied ultrasound time of 30, 60, 90 and 120 s, respectively. In addition, the cell proliferation inhibition assay showed the cell viability of targeted PTX-loaded MBs was significantly lower than that of non-targeted PTX-loaded MBs and non-targeted unloaded MBs when ultrasound was utilized. In conclusion, the study indicated the LyP-1-coated PTX-loaded MBs significantly increased the antitumor efficacy and can be used as a potential chemotherapy approach for ultrasound-assisted breast cancer treatment.