In vivo assessment of apoptotic response to cancer therapy is believed to be very important for optimizing management of treatment. However, few noninvasive strategies are currently available to monitor the therapeutic response in vivo. Ultrasonography has been used to detect apoptotic cell death in vivo, but a high-frequency transducer is needed. Fortunately, the capability of ultrasound contrast agents (UCAs) to exit the leaky vasculature of tumors enables ultrasound-targeted imaging of molecular events in response to cancer therapy. In this study, we prepared a novel nano-sized UCA, namely, Annexin V-conjugated nanobubbles (AV-NBs, 635.5 ± 25.4 nm). In vitro studies revealed that AV-NBs were relatively stable and highly echogenic. Moreover, these AV-NBs could easily extravasate into the tumor vasculature and recognize the apoptotic cells with high specificity and affinity in tumors sensitive to chemotherapy. Ultrasound imaging results demonstrated that AV-NBs had higher echogenicity and significantly greater enhancement compared with the untargeted control NBs (P < 0.01) inside the tumors after chemotherapy. Taken together, this study provides a promising method to accurately evaluate therapeutic effects at the molecular level to support cancer management.

据信对癌症治疗的凋亡反应的体内评估对于优化治疗管理非常重要。然而，目前很少有非侵入性策略可用于监测体内的治疗反应。超声已经被用于检测体内凋亡细胞的死亡，但是需要一个高频换能器。幸运的是，超声造影剂（UCA）退出肿瘤渗漏的脉管系统的能力使响应于癌症治疗的分子事件的超声靶向成像成为可能。在这项研究中，我们制备了一种新型的纳米级UCA，即膜联蛋白V共轭的纳米气泡（AV-NBs，635.5±25.4 nm）。体外研究表明，AV-NB具有相对的稳定性和高回声性。此外，这些AV-NBs容易渗入肿瘤血管，并在对化疗敏感的肿瘤中以高特异性和亲和力识别凋亡细胞。超声成像结果表明，与 化疗后肿瘤内未靶向的对照NB相比，AV-NB具有更高的回声性和明显更大的增强作用（P <0.01）。两者合计，这项研究提供了一种有前途的方法，可以在分子水平上准确评估治疗效果以支持癌症治疗。