The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells. Furthermore, the effects of drug loaded microbubbles on neovascularization and tumor cells were studied. The tumor vascular targeted and ultrasound-responsive microbubbles of 5-FU@DLL4-MBs were prepared by the thin-film dispersion method. The size and zeta potential of 5-FU@DLL4-MBs was about 1248 nm and −9.1 mV. 5-FU@DLL4-MBs released 5-FU showed an ultrasound-responsive manner, and had better vascular-targeting ability. Furthermore, the 5-FU@DLL4-MBs showed the strongest cytotoxic effect on HUVECs or HepG-2 cells and can be effectively internalized into the HUVECs cells. Thus, 5-FU@DLL4-MBs combined with HIFU can be considered as a potential method for antitumor angiogenesis in the future.

抗新生血管治疗是肿瘤分子靶向治疗的有效策略之一。目前，抗血管形成治疗的目标和效果有限，迫切需要建立新的血管靶向治疗策略来有效治疗肿瘤。在这项工作中，我们使用高强度聚焦超声（HIFU）与靶向微泡相结合，为新血管细胞建立了分子靶向超声响应微泡。此外，研究了载药微泡对新血管形成和肿瘤细胞的作用。通过薄膜分散法制备5-FU @ DLL4-MBs的肿瘤血管靶向和超声响应微泡。5-FU @ DLL4-MBs的大小和zeta电位约为1248 nm和-9.1 mV。释放的5-FU @ DLL4-MBs 5-FU显示出超声响应方式，并且具有更好的血管靶向能力。此外，5-FU @ DLL4-MBs对HUVEC或HepG-2细胞显示出最强的细胞毒性作用，可以有效地内化到HUVECs细胞中。因此，5-FU @ DLL4-MBs与HIFU结合可被认为是未来抗肿瘤血管生成的潜在方法。