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首页> 外文期刊>Nanotoxicology >Bioengineered gold nanoparticles targeted to mesenchymal cells from patients with bronchiolitis obliterans syndrome does not rise the inflammatory response and can be safely inhaled by rodents
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Bioengineered gold nanoparticles targeted to mesenchymal cells from patients with bronchiolitis obliterans syndrome does not rise the inflammatory response and can be safely inhaled by rodents

机译：针对患有支气管炎患者的模间密度细胞的生物工程金纳米颗粒综合征不会升高炎症反应，可以通过啮齿动物安全吸入

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The use of gold nanoparticles (GNPs) as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long-term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favors epithelial-mesenchymal transition and activation of local mesenchymal cells (MCs) leading to airway fibroobliteration. In a previous work, we engineered GNPs loaded with the mammalian target of rapamycin inhibitor everolimus, specifically decorated with an antibody against CD44, a surface receptor expressed by primary MCs isolated from bronchoalveolar lavage of BOS patients. We proved in vitro that these GNPs (GNP-HCe) were able to specifically inhibit primary MCs without affecting the bronchial epithelial cell. In the present work, we investigated the effect of these bioengineered nanoconstructs on inflammatory cells, given that a stimulating effect on macrophages, neutrophils or lymphocytes is strongly unwanted in graft airways since it would foster fibrogenesis. In addition, we administered GNP-HCe by the inhalatory route to normal mice for a preliminary assessment of their pulmonary and peripheral (liver, spleen and kidney) uptake. By these experiments, an evaluation of tissue toxicity was also performed. The present study proves that our bioengineered nanotools do not rise an inflammatory response and, under the tested inhalatory conditions that were used, are non-toxic.
机译：使用金纳米颗粒（GNP）作为药物递送系统代表了由于局部药物积累不足和过度的全身毒性而没有有效药理学治疗的疾病的有希望的问题。支气管炎梗阻综合征（BOS）代表约70％的慢性肺同种异体移植功能障碍，是长期肺移植的主要挑战。据信，由于对上皮支气管细胞的重复损伤，局部炎症反应产生了一种融合上皮 - 间充质转换和激活局部充质细胞（MCS）的Milieu，导致气道纤维纤维斑块纤维纤维斑块。在以前的工作中，我们用哺乳动物抑制剂everolimus的哺乳动物靶标设计了GNP，具体用针对CD44的抗体装饰，由博斯患者的支气管血管灌洗中分离的原发性MCS表达的表面受体。我们证明了这些GNP（GNP-HCE）能够特异性地抑制原发性MCS而不影响支气管上皮细胞。在目前的工作中，考虑到对巨噬细胞，中性粒细胞或淋巴细胞对移植气道的刺激作用强烈不希望，因此研究了这些生物工程纳米结构对炎性细胞的影响，因为它将促进纤维发生。此外，我们通过对正常小鼠进行的术语途径给予GNP-HCE，以初步评估其肺和外周（肝，脾和肾）摄取。通过这些实验，还进行了组织毒性的评估。本研究证明，我们的生物工程纳米机不能上升炎症反应，并且在所使用的测试中，无毒。

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