Department of Industrial and Physical Pharmacy, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
Biomacromolecules. 2013 Jul 8;14(7):2389-95. doi: 10.1021/bm400512g. Epub 2013 Jun 5.
Nanometer-sized drug carriers including polymeric nanoparticles (NPs) have been used to increase biodistribution of a drug in tumors, thereby reducing the effective dose of chemotherapy. NPs increase drug delivery to tumors to a certain extent, but the amount reaching tumors is only a small fraction of the total administered NPs because they depend on passive accumulation via the leaky vasculature surrounding tumors. In an attempt to further increase the drug delivery to tumors, we develop a polymeric NP system that interacts with an endothelial tumor marker. The NPs are decorated with quinic acid, a synthetic mimic of sialyl Lewis-x, which binds to E-selectin, overexpressed on the surface of endothelial cells surrounding solid tumors. The NPs selectively bind to endothelial cells activated with tumor necrosis factor-α, with weak affinity at a relatively high shear stress. These properties may help NPs reach tumors by increasing the encounter of NPs with the peritumoral endothelium without hindering subsequent transport of the NPs.
纳米级药物载体，包括聚合物纳米颗粒（NPs），已被用于增加药物在肿瘤中的分布，从而降低化疗的有效剂量。NPs 在一定程度上增加了药物向肿瘤的输送，但到达肿瘤的数量仅占给予的 NPs 总量的一小部分，因为它们依赖于通过肿瘤周围渗漏的血管被动积累。为了进一步增加药物向肿瘤的输送，我们开发了一种与内皮肿瘤标志物相互作用的聚合物 NP 系统。NPs 用奎尼酸修饰，这是唾液酸 Lewis-x 的合成模拟物，与肿瘤周围内皮细胞表面过度表达的 E-选择素结合。NPs 选择性地与肿瘤坏死因子-α激活的内皮细胞结合，在相对较高的剪切应力下具有较弱的亲和力。这些特性可能有助于 NPs 通过增加与肿瘤周围内皮细胞的接触来到达肿瘤，而不会阻碍随后 NPs 的运输。
