基于聚乳酸立体复合物的高弹性纳米囊状超声造影剂

As one of primary imaging techniques, ultrasonography is versatile, noninvasive, portable, low cost and risk in clinical diagnosis. In many cases, some high impedance substances, namely ultrasound contrast agent (UCA), are administered to patientswithin the highly vascular region just for strong constrast effect between the lesions and background organs or tissues. So these UCAs can facilitate “clearer” image and effectively increase the diagnostic yield. However, the low stability and too short retention time of UCAs still remain unsolved, even if novel UCAs represented by nanobubble, nanucapsule and so on, are emerging in an endless stream. As a result, we utilize poly(lactic acid) stereocomplex and liquid-gas phase transition fluorocarbon to construct solid and sellf-assembled nanocapsule configurations with high strength, elasticity, constrast and narrow particle size distribution. And theire mechnical properties will be exactly measured by the echo signal in free state and settled ultrasound field, to provide solid evidences for subsequent envaluation on stability and imaging effect. Our study is anticipated to greatly improve the effectiveness and applicability of UCA, and to widen the application of UCA in tumor diagnosis and intraoperative real-time monitoring. And it can also provide an efficient and accurate detection method for mechnical stability of UCAs and other micro-/nanoparticles.

超声扫描成像技术以其通用、无创、实时、便携、低成本、低风险等显著优势，被广泛应用于临床医学诊断。大多数情况下，一些高阻抗物质，即超声造影剂，会被注射到患者体内血管丰富区域，以增强兴趣区与背景组织或器官的对比效果，从而获得更加清晰的诊断图像以提高诊断率。然而截至目前，以纳米泡、纳米囊等为代表的众多新型超声造影剂尚未解决其声场稳定性差、持续时间短的关键成像问题。因此，本课题利用聚乳酸立体复合物和液-气相转变氟碳构建了一种兼具高强度、高弹性、高对比度和窄分布的纳米自组装囊状结构，并通过固定声场和自由状态下该纳米粒子的回波信号测算其结构的特征力学常数，为后期体内外造影效果的综合评价提供准确的稳定性判据。其预期成果将极大地提高超声造影剂的实效性和适用性，开拓其在肿瘤诊断和手术实时监测中的应用，同时也为超声造影剂及其它微纳米粒子的力学稳定性评价提供一种高效、准确的新方法。

超声扫描成像技术以其通用、无创、实时、便携、低成本、低风险等显著优势，被广泛应用于临床医学诊断。大多数情况下，一些高阻抗物质，即超声造影剂，会被注射到患者体内血管丰富区域，以增强兴趣区与背景组织或器官的对比效果，从而获得更加清晰的诊断图像以提高诊断率。然而截至目前，以纳米泡、纳米囊等为代表的众多新型超声造影剂尚未解决其声场稳定性差、持续时间短的关键成像问题。因此，本项目通过二次乳化和氟碳端基诱导的聚合物协同自组装法，利用聚乳酸立体复合物和液-气相转变的40°C沸点七氟-2-碘代丙烷构建了一种兼具高强度、高弹性、高对比度和窄分布的纳米囊状结构。测试结果表明，该方法可明显提高纳米囊壳层聚乳酸嵌段的结晶度和立体复合程度，由此得到的纳米囊具有远高于普通聚乙二醇-b-聚乳酸纳米囊的力学强度和弹性。由于低沸点液态氟碳内核的存在，该纳米囊在较高温度的水相环境中表现出显著增强的超声成像效果。该成果将有望实现低强度诊断超声条件下的可控持久成像，甚至肿瘤核心高温区域的被动靶向成像，从而极大地提高超声造影剂的实效性和适用性，开拓其在肿瘤诊断和手术实时监测中的应用。