Department of Biomedical Engineering , Boston University , 44 Cummington Mall , Boston , Massachusetts 02215 , United States.
Laboratoire de Microfluidique, MEMS et Nanostructures , ESPCI Paris , PSL Research University, Institut Pierre Gilles de Gennes (IPGG), CNRS (CBI), 6 rue Jean Calvin , 75005 Paris , France.
Langmuir. 2019 Aug 6;35(31):10061-10067. doi: 10.1021/acs.langmuir.8b03692. Epub 2019 Feb 8.
The development of new therapies for surgical adhesions has proven to be difficult as there is no consistently effective way to assess treatment efficacy in clinical trials without performing a second surgery, which can result in additional adhesions. We have developed lipid microbubble formulations that use a short peptide sequence, CREKA, to target fibrin, the molecule that forms nascent adhesions. These targeted polymerized shell microbubbles (PSMs) are designed to allow ultrasound imaging of early adhesions for diagnostic purposes and for evaluating the success of potential treatments in clinical trials while acting as a possible treatment. In this study, we show that CREKA-targeted microbubbles preferentially bind fibrin over fibrinogen and are stable for long periods of time (∼48 h), that these bound microbubbles can be visualized by ultrasound, and that neither these lipid-based bubbles nor their diagnostic-ultrasound-induced vibrations damage mesothelial cells in vitro. Moreover, these bubbles show the potential to identify adhesionlike fibrin formations and may hold promise in blocking or breaking up fibrin formations in vivo.
开发用于手术粘连的新疗法已被证明颇具难度，因为在不进行第二次手术的情况下，临床试验中没有始终有效的方法来评估治疗效果，而第二次手术可能会导致更多的粘连。我们开发了脂质微泡制剂，该制剂使用短肽序列 CREKA 来靶向纤维蛋白，即形成新生粘连的分子。这些靶向聚合壳微泡 (PSM) 的设计目的是允许超声成像用于早期粘连的诊断目的，并用于评估临床试验中潜在治疗方法的成功，同时作为一种可能的治疗方法。在这项研究中，我们表明，CREKA 靶向的微泡优先结合纤维蛋白而不是纤维蛋白原，并且稳定的时间较长（约 48 小时），这些结合的微泡可以通过超声进行可视化，并且这些基于脂质的气泡及其诊断超声诱导的振动都不会损害体外的间皮细胞。此外，这些气泡具有识别类似粘连的纤维蛋白形成的潜力，并可能有希望在体内阻止或破坏纤维蛋白形成。
