Tumour targeted contrast enhanced ultrasound imaging dual-modal microbubbles for diagnosis and treatment of triple negative breast cancer

Abstract

At present, the treatment of triple negative breast cancer (TNBC) is a worldwide problem, urgently requiring early precise diagnosis and effective treatment methods. In our study, we designed a type of tumour targeted dual-modal microbubbles, paclitaxel (PTX)-loaded RGD-lipid microbubbles (PTX@RGD-MBs), combined with ultrasonic targeted microbubble destruction (UTMD) to precisely diagnose TNBC and to improve the curative effect. As the first-line drug, PTX, lacking specific tumour targeting and the ability to be effectively internalized by TNBC cells, is still not effective in killing TNBC cells. For this reason, we used the tumour active targeting peptide RGD to precisely guide MBs around TNBC cells through the high affinity to the integrin α_vβ₃ receptor, and use UTMD to generate shear stress on cells to open transient pores in the cellular membrane, so as to improve MB penetration into the cellular membrane. Sulfur hexafluoride (SF₆) as the internal gas of MBs can greatly improve the resolution and sensitivity of conventional US images through nonlinear harmonics to enhance the comparison between lesions and surrounding normal tissues. The results in our study demonstrated that RGD-MBs with UTMD were internalized by TNBC cells more effectively, leading to significant increase in intercellular drug concentrations of TNBC cells, thus achieving the best inhibitory effect on TNBC cells in vitro. Ultrasonic experiment showed that PTX@RGD-MBs produced high quality contrast enhanced ultrasound (CEUS) images in vitro and in vivo, providing a better method for diagnosis and evaluation of the TNBC. Therefore, we conclude the advantages of excellent anti-tumour effect and CEUS imaging of PTX@RGD-MBs provided a better application for diagnosis and treatment of TNBC.