Polymeric contrast agent with targeting potential
Polymeric contrast agent with targeting potential
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具有靶向潜力的聚合物造影剂。
DOI：
10.1016/j.ultras.2003.12.018
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发表时间：
2004-04-01
期刊：
影响因子：
4.2
通讯作者：
Wheatley, MA
中科院分区：
文献类型：
--
作者：
Lathia, JD;Leodore, L;Wheatley, MA
将Arg-Gly-Asp （RGD）肽序列偶联到聚乳酸（PLA）微胶囊上。这些中空的，可生物降解的聚乳酸微胶囊是在我们的实验室开发的，用作超声造影剂。通过用靶向配体修饰药物的表面，它可以被靶向到体内的特定地址。该应用程序是理想的靶向成像和/或靶向药物输送。整合素是细胞中的跨膜蛋白，在细胞附着和许多其他过程中起着至关重要的作用。RGD肽序列靶向血管生成过程中表达的整合素，α (V) β(3)和α (V) β(5)。血管生成特异性整合素在癌症期间更活跃，可以用作rgd偶联造影剂的受体。尽管通用RGD序列并非仅针对α (V) β(3)和α (V) β(5)整合素，但它是这里描述的概念证明研究的绝佳候选者。初步体外实验结果表明，修饰后的胶囊在体外保持高回声（最大增强20 dB），并在静态实验中特异性粘附于乳腺癌细胞系MDA-MB-231。然而，未修饰的胶囊（阴性对照）或与RGD配体预饱和的细胞接触修饰的胶囊（阳性对照）均未见粘附性。超声造影剂的特异性靶向可以引导成像的方式作为恶性和良性区分的方法。(C) 2003 Elsevier B.V.版权所有
The Arg-Gly-Asp (RGD) peptide sequence was conjugated to poly (lactid acid), (PLA), microcapsules. These hollow, biodegradable PLGA microcapsules were developed in our laboratory for use as ultrasound contrast agents. By modifying the surface of the agent with a targeting ligand, it Can be targeted to a specific address within the body. This application is ideal for both targeted imaging and/or targeted drug delivery. Integrins are membrane-spanning proteins in cells that play a vital role in cell attachment and many other processes. The RGD peptide sequence targets integrins expressed during angiogenesis, alpha(V)beta(3) and alpha(V)beta(5). The integrins specific to angiogenesis are more active during cancer and can be used as receptors for the RGD-conjugated contrast agents. Although the generic RGD sequence is not specific to only alpha(V)beta(3) and alpha(V)beta(5) integrins, it is ail excellent candidate for proof of concepts studies such as described here.Preliminary in vitro results indicate that the modified capsules remain highly echogenic (maximum enhancement of 20 dB in vitro) and adhere specifically to a breast cancer cell line MDA-MB-231 in static experiments. However, no adherence is seen with either unmodified capsules (negative control), or when cells that have been pre-saturated with RGD ligand are contacted with modified capsules (positive control). Specific targeting of ultrasound contrast agents could lead the way to imaging as a method for discrimination of malignant from benign. (C) 2003 Elsevier B.V. All rights reserved.