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Fibrin-Targeted Polymerized Shell Microbubbles as Potential Theranostic Agents for Surgical Adhesions

机译:靶向纤维蛋白的聚合壳微泡作为外科粘连的潜在治疗药物

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摘要

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.
机译:由于没有始终如一的有效方法来评估临床试验中的治疗效果,而不进行第二次手术,这可能会导致额外的粘连,因此,开发用于手术粘连的新疗法已被证明是困难的。我们已经开发出脂质微泡制剂,该制剂使用短肽序列CREKA靶向形成初生粘附的分子纤维蛋白。这些靶向的聚合壳微泡(PSM)旨在允许对早期粘连进行超声成像,以用于诊断目的并评估临床试验中潜在治疗的成功,同时作为可能的治疗方法。在这项研究中,我们表明,以CREKA为靶点的微泡比血纤蛋白原优先结合血纤蛋白,并且在长时间(〜48小时)内稳定,这些结合的微泡可通过超声观察,并且这些脂质基泡或它们的脂质诊断超声诱发的振动会在体外损害间皮细胞。而且,这些气泡显示出识别粘附样纤维蛋白形成的潜力,并且在体内阻断或破坏纤维蛋白形成方面具有希望。

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