INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
CNRS UMR5629, Laboratoire de Chimie des Polymères Organiques, Pessac, France; Univ. Bordeaux, Bordeaux-INP, Grenoble, France.
Nanomedicine. 2016 May;12(4):921-932. doi: 10.1016/j.nano.2015.11.018. Epub 2015 Dec 24.
New approaches that are more efficient and able to specifically reach lung tumors are needed. We developed new hyaluronan-based nanoparticles targeting CD44 receptors of two different sizes and compared their lung cancer cells targeting efficacy in vitro and in vivo. The nanoparticles' cellular uptake was dose-dependent, and specific to hyaluronan receptors, particularly CD44. The binding and internalization differed according to nanoparticle size. In vivo biodistribution studies in two orthotopic lung tumor models showed that intrapulmonary nebulized nanoparticles accumulated in lungs, but not in the tumor nodules. In contrast, despite a significant liver capture, intravenous injection led to a better accumulation of the nanoparticles in the lung tumors compared with the surrounding healthy lung tissues. We demonstrated that the hyaluronan-based nanoparticles size plays significant role in cellular uptake and biodistribution. Small nanoparticles showed active targeting of CD44-overexpressing tumors, suggesting that they could be used as drug-delivery system.
Combating cancers remains an important goal in clinical medicine. In this study, the authors investigated the ability of two hyaluronan-based nanoparticles targeting CD44 receptors to home in on lung cancer cells in an in-vivo orthotropic model. The preferential uptake of smaller sized nanoparticles via intravenous route has further enhanced the existing knowledge of future drug designs.
需要新的方法,这些方法更有效,能够专门针对肺部肿瘤。我们开发了两种不同大小的靶向 CD44 受体的新型透明质酸纳米颗粒,并比较了它们在体外和体内对肺癌细胞的靶向效果。纳米颗粒的细胞摄取呈剂量依赖性,并且对透明质酸受体,特别是 CD44 具有特异性。结合和内化根据纳米颗粒的大小而不同。在两种原位肺癌肿瘤模型的体内生物分布研究中,经肺内雾化的纳米颗粒积聚在肺部,但不在肿瘤结节中。相比之下,尽管肝脏摄取量很大,但与周围健康肺组织相比,静脉注射导致纳米颗粒在肺肿瘤中的积累更好。我们证明了透明质酸基纳米颗粒的大小在细胞摄取和生物分布中起着重要作用。小纳米颗粒显示出对 CD44 过表达肿瘤的主动靶向,表明它们可用作药物递送系统。
对抗癌症仍然是临床医学的一个重要目标。在这项研究中,作者研究了两种靶向 CD44 受体的透明质酸纳米颗粒在体内原位模型中靶向肺癌细胞的能力。通过静脉途径优先摄取较小的纳米颗粒进一步增强了未来药物设计的现有知识。