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通过静脉途径在BALB/c小鼠中安全给药碳纳米管。

Safe Administration of Carbon Nanotubes by Intravenous Pathway in BALB/c Mice.

作者信息

Guzmán-Mendoza Jesús, Montes-Fonseca Silvia Lorena, Ramos-Martínez Ernesto, González-Horta Carmen, Hernández-Rodríguez Pilar Del Carmen, Orrantia-Borunda Erasmo, Chávez-Flores David, Sánchez-Ramírez Blanca

机构信息

Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua. Circuito No. 1 Campus Universitario II, Chihuahua CP 31125, México.

Instituto Tecnológico de Monterrey Campus Chihuahua, Heroico Colegio Militar 4700, Col. Nombre de Dios, Chihuahua CP 31300, México.

出版信息

Nanomaterials (Basel). 2020 Feb 24;10(2):400. doi: 10.3390/nano10020400.

Abstract

Carbon nanotubes (CNTs) are nanomaterials with multiple possible uses as drug carriers or in nanovaccine development. However, the toxicity of CNTs administered intravenously in models has not been fully described to date. This work aimed to evaluate the toxic effect of pristine multi-walled CNTs (UP-CNTs), purified (P-CNTs), or CNTs functionalized with fluorescein isothiocyanate (FITC-CNTs) administered by intravenous injection in BALB/c mice. Biochemical and histopathological parameters were analyzed at 1, 14, 29, and 60 days post-exposure. Pristine CNTs were the most toxic nanoparticles in comparison with P-CNTs or FITC-CNTs, increasing serum AST (≈ 180%), ALT (≈ 300%), and LDH (≈ 200%) levels at one day post-exposure. The urea/creatinine ratio suggested pre-renal injury at the 14 day accompanied of extensive lesions in kidneys, lungs, and liver. Biochemical and histological findings in mice exposed to P-CNTs had not significant differences compared to the controls. A lower toxic effect was detected in animals exposed to FITC-CNTs which was attributable to FITC toxicity. These results demonstrate that the purification process of CNTs reduces toxicity, and that toxicity in functionalized CNTs is dependent on the functionalized compound. Therefore, P-CNTs are postulated as potential candidates for safe biomedical applications using an intravenous pathway.

摘要

碳纳米管(CNTs)是一类纳米材料,在药物载体或纳米疫苗研发方面有多种潜在用途。然而,迄今为止,静脉注射碳纳米管在动物模型中的毒性尚未得到充分描述。本研究旨在评估静脉注射原始多壁碳纳米管(UP-CNTs)、纯化碳纳米管(P-CNTs)或异硫氰酸荧光素功能化碳纳米管(FITC-CNTs)对BALB/c小鼠的毒性作用。在暴露后1天、14天、29天和60天分析生化和组织病理学参数。与P-CNTs或FITC-CNTs相比,原始碳纳米管是毒性最强的纳米颗粒,暴露后1天血清谷草转氨酶(AST)(约升高180%)、谷丙转氨酶(ALT)(约升高300%)和乳酸脱氢酶(LDH)(约升高200%)水平升高。尿素/肌酐比值表明在第14天出现肾前性损伤,并伴有肾脏、肺和肝脏的广泛病变。与对照组相比,暴露于P-CNTs的小鼠的生化和组织学结果没有显著差异。在暴露于FITC-CNTs的动物中检测到较低的毒性作用,这归因于FITC的毒性。这些结果表明,碳纳米管的纯化过程降低了毒性,功能化碳纳米管的毒性取决于功能化化合物。因此,P-CNTs被认为是通过静脉途径进行安全生物医学应用的潜在候选材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613f/7075304/e6430ca6e26a/nanomaterials-10-00400-g001.jpg

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