Multifunctional polyurethane-urea nanoparticles to target and arrest inflamed vascular environment: A potential tool for cancer therapy and diagnosis
Multifunctional polyurethane-urea nanoparticles to target and arrest inflamed vascular environment: A potential tool for cancer therapy and diagnosis
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DOI：
10.1016/j.jconrel.2013.06.027
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发表时间：
2013-10-28
影响因子：
10.8
通讯作者：
Garcia-Celma, M. J.
中科院分区：
文献类型：
--
作者：
Morral-Ruiz, G.;Melgar-Lesmes, P.;Garcia-Celma, M. J.
内皮细胞炎症通路的激活有助于多种人类癌症的肿瘤生长和进展。细胞粘附分子参与白细胞向血管炎症环境的募集，在血管生成、抑制凋亡、增殖、侵袭和转移中起着关键作用。我们在这里描述了链霉亲素涂层聚氨酯-尿素纳米颗粒的发展，作为荧光成像或肿瘤环境靶向的多功能纳米载体，以识别和阻止灌溉肿瘤组织的血管网络。这些多功能纳米颗粒的设计包括将链霉亲和素结合到纳米颗粒聚合物基质中。得到的纳米颗粒呈球形，平均直径为70-74 nm。链霉亲和素包被的纳米颗粒可以自发结合生物素化的抗VCAM-1和ICAM-1的抗体，这些抗体在体外和体内特异性地附着在发炎的内皮细胞上。事实上，将CBO-P11（一种血管内皮生长因子促血管生成和促炎症途径的特异性抑制剂）掺入这些纳米颗粒中，可以产生靶向药理作用，从而仅在炎症内皮细胞中减少增殖。本文描述的多种功能化策略可以用于肿瘤诊断或靶向药物输送到肿瘤血管，具有良好的安全性和一系列有吸引力的生物医学应用的可能性。(C) 2013 Elsevier b.v.版权所有
Activation of inflammatory pathways in endothelial cells contributes to tumour growth and progression in multiple human cancers. Cellular adhesion molecules are involved in leukocyte recruitment to the vascular inflammatory environment where it plays a critical role in angiogenesis, suppression of apoptosis, proliferation, invasion and metastasis. We describe here the development of streptavidin-coated polyurethane-urea nanoparticles as multifunctional nanocarriers for fluorescence imaging or targeting of the tumour environment to identify and arrest the vascular network irrigating the tumour tissue. The design of these multifunctional nanoparticles involves incorporating streptavidin to the nanoparticle polymeric matrix. The obtained nanoparticles are spherical and exhibit an average diameter of 70-74 nm. Streptavidin-coated nanoparticles spontaneously bind biotinylated antibodies against VCAM-1 and ICAM-1 which in vitro and in vivo specifically attached to inflamed endothelial cells. Indeed the incorporation of CBO-P11 (a specific inhibitor of the vascular endothelial growth factor proangiogenic and proinflammatory pathway) to these nanoparticles allows a targeted pharmacological effect thereby decreasing the proliferation only in inflamed endothelial cells. The multiple functionalisation strategy described here could be exploited for tumour diagnostics or targeted drug delivery to tumour vasculature with a good safety profile and an attractive array of possibilities for biomedical applications. (C) 2013 Elsevier B. V. All rights reserved.