Zha R Helen, Sur Shantanu, Boekhoven Job, Shi Heidi Y, Zhang Ming, Stupp Samuel I
Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208, USA; Simpson Querrey Institute for BioNanotechnology, Northwestern University, 303 East Superior Street, Lurie Suite 11-131, Chicago, IL 60611, USA.
Simpson Querrey Institute for BioNanotechnology, Northwestern University, 303 East Superior Street, Lurie Suite 11-131, Chicago, IL 60611, USA.
Acta Biomater. 2015 Jan;12:1-10. doi: 10.1016/j.actbio.2014.11.001. Epub 2014 Nov 8.
Aberrant angiogenesis plays a large role in pathologies ranging from tumor growth to macular degeneration. Anti-angiogenic proteins have thus come under scrutiny as versatile, potent therapeutics but face problems with purification and tissue retention. We report here on the synthesis of supramolecular nanostructures that mimic the anti-angiogenic activity of maspin, a class II tumor suppressor protein. These maspin-mimetic nanostructures are formed via self-assembly of small peptide amphiphiles containing the g-helix motif of maspin. Using tubulogenesis assays with human umbilical vein endothelial cells, we demonstrate that maspin-mimetic nanostructures show anti-angiogenic activity at concentrations that are significantly lower than those necessary for the g-helix peptide. Furthermore, in vivo assays in the chick chorioallantoic membrane show maspin-mimetic nanostructures to be effective over controls at inhibiting angiogenesis. Thus, the nanostructures investigated here offer an attractive alternative to the use of anti-angiogenic recombinant proteins in the treatment of cancer or other diseases involving abnormal blood vessel formation.
异常血管生成在从肿瘤生长到黄斑变性等多种病理过程中起着重要作用。因此，抗血管生成蛋白作为一种多功能、强效的治疗药物受到了密切关注，但在纯化和组织保留方面面临问题。我们在此报告了超分子纳米结构的合成，该结构模拟了II类肿瘤抑制蛋白maspin的抗血管生成活性。这些模拟maspin的纳米结构是通过含有maspin的g-螺旋基序的小肽两亲分子的自组装形成的。使用人脐静脉内皮细胞的管形成试验，我们证明模拟maspin的纳米结构在浓度显著低于g-螺旋肽所需浓度时就显示出抗血管生成活性。此外，在鸡胚绒毛尿囊膜上的体内试验表明，模拟maspin的纳米结构在抑制血管生成方面比对照更有效。因此，本文研究的纳米结构为在治疗癌症或其他涉及异常血管形成的疾病中使用抗血管生成重组蛋白提供了一种有吸引力的替代方案。
