Bai Min, Dong Yang, Huang Hui, Fu Hao, Duan Yourong, Wang Qi, Du Lianfang
Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200080 China
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200032 China.
RSC Adv. 2019 Feb 15;9(10):5682-5691. doi: 10.1039/c8ra09737b. eCollection 2019 Feb 11.
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 αβ 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 (SF) 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 . Ultrasonic experiment showed that PTX@RGD-MBs produced high quality contrast enhanced ultrasound (CEUS) images and , 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.
目前，三阴性乳腺癌（TNBC）的治疗是一个全球性难题，迫切需要早期精准诊断和有效的治疗方法。在我们的研究中，我们设计了一种肿瘤靶向双模态微泡，即负载紫杉醇（PTX）的RGD脂质微泡（PTX@RGD-MBs），并结合超声靶向微泡破坏（UTMD）技术来精准诊断TNBC并提高治疗效果。作为一线药物，PTX缺乏特异性肿瘤靶向性且无法被TNBC细胞有效内化，在杀伤TNBC细胞方面仍然效果不佳。因此，我们利用肿瘤活性靶向肽RGD通过与整合素αβ受体的高亲和力将微泡精准导向TNBC细胞周围，并利用UTMD在细胞上产生剪切应力以在细胞膜上打开瞬时孔隙，从而提高微泡穿透细胞膜的能力。六氟化硫（SF）作为微泡的内部气体，可通过非线性谐波极大地提高传统超声图像的分辨率和灵敏度，增强病变与周围正常组织之间的对比度。我们的研究结果表明，UTMD处理后的RGD-MBs能更有效地被TNBC细胞内化，导致TNBC细胞内药物浓度显著增加，从而对TNBC细胞产生最佳抑制效果。超声实验表明，PTX@RGD-MBs能产生高质量的超声造影（CEUS）图像，为TNBC的诊断和评估提供了更好的方法。因此，我们得出结论，PTX@RGD-MBs具有优异的抗肿瘤效果和CEUS成像优势，为TNBC的诊断和治疗提供了更好的应用前景。
