The Interactions between L-tyrosine based nanoparticles decorated with folic acid and cervical cancer cells under physiological flow.
The Interactions between L-tyrosine based nanoparticles decorated with folic acid and cervical cancer cells under physiological flow.
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DOI：
10.1021/mp300221f
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发表时间：
2012-11-05
影响因子：
4.9
通讯作者：
Yun YH
中科院分区：
文献类型：
--
作者：
Ditto AJ;Shah KN;Robishaw NK;Panzner MJ;Youngs WJ;Yun YH
许多抗癌药物已在临床上确立，但其疗效可能会因非特异性毒性和无法到达所需的癌性细胞内空间而受到损害。为了解决这些问题，研究人员探索了使用叶酸作为靶向部分来提高化疗药物的特异性。为了扩展此类研究，我们将叶酸与功能化聚乙二醇结合，随后装饰 L-酪氨酸多磷酸 (LTP) 纳米粒子的表面。如扫描电子显微镜和动态光散射所示，这些纳米颗粒具有适合内化的尺寸（100-500 nm）。在模拟生理流下，与对照纳米颗粒和人类真皮成纤维细胞相比，用叶酸修饰的 LTP 纳米颗粒（靶向纳米颗粒）对宫颈癌细胞系 HeLa 的附着力高出 10 倍。这些目标纳米颗粒的附着以线性速率进行，并且该纳米颗粒附着的强度显示可承受 3.0 达因/厘米 2 的剪切应力。靶向纳米颗粒与 HeLa 的这些相互作用可能是受体-配体结合的结果，因为与游离叶酸的竞争研究抑制了纳米颗粒的附着。最后，与未修饰的（普通）纳米颗粒和单独的药物相比，用银基药物封装的靶向纳米颗粒对 HeLa 细胞显示出更高的功效。因此，靶向纳米粒子是开发过度表达叶酸受体（FR）的抗癌疗法的有前途的递送平台。
Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of L-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100–500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dynes/cm2. These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to non-decorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that over-express the folate receptors (FRs).
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