Lacerda Lara, Ali-Boucetta Hanene, Herrero Maria A, Pastorin Giorgia, Bianco Alberto, Prato Maurizio, Kostarelos Kostas
The School of Pharmacy, University of London, Nanomedicine Laboratory, Centre for Drug Delivery Research, London WC1N 1AX, UK.
Nanomedicine (Lond). 2008 Apr;3(2):149-61. doi: 10.2217/17435889.3.2.149.
Carbon nanotubes (CNTs) constitute one of the most important types of nanomaterials, increasingly gaining interest as tools for nanomedicine applications, such as sensors, implants or delivery systems. Our groups have reported previously that chemical functionalization of CNTs can lead to their almost complete elimination from the body of animals through the urinary excretion route. The administration of CNTs may, however, impact the physiological function of organs through which CNTs traverse or accumulate.
The present study addresses the short-term impact (first 24 h) of intravenous administration of various types of multiwalled nanotubes (MWNTs) on the physiology of healthy mice.
MATERIALS & METHODS: Nonfunctionalized, purified MWNTs (pMWNTs) and different types of water-dispersible, functionalized MWNTs (f-MWNTs) were tail-vein injected. Histological examination of tissues (kidney, liver, spleen and lung) harvested 24 h post-administration indicated that organ accumulation depended on the degree of ammonium (NH(3)(+)) functionalization at the f-MWNT surface.
The higher the degree of functionalization of MWNT-NH(3)(+), the less their accumulation in tissues. pMWNTs coated with autologous serum proteins prior to injection accumulated almost entirely in the lung and liver in large dark clusters. Moreover, various indicators of serum and urine analyses also confirmed that MWNT-NH(3)(+) injections did not induce any physiological abnormality in all major organs within the first 24 h post-injection. Interestingly, no abnormalities were observed either for f-MWNTs highly functionalized with carboxylate groups (diethylentriaminepentaacetic-functionalized MWNTs) or by upscaling to the highest doses ever injected so far in vivo (20 mg/kg).
The high degree of f-MWNT functionalization responsible for adequate individualization of nanotubes and not the nature of the functional groups was the critical factor leading to less tissue accumulation and normal tissue physiology at least within the first 24 h post-administration, even at the highest carbon nanotube doses ever administered in any study today.
碳纳米管(CNTs)是最重要的纳米材料类型之一,作为纳米医学应用工具,如传感器、植入物或递送系统,越来越受到关注。我们的研究小组之前报道过,碳纳米管的化学功能化可使其通过尿液排泄途径几乎完全从动物体内清除。然而,碳纳米管的给药可能会影响其穿过或积聚的器官的生理功能。
本研究探讨静脉注射各种类型的多壁纳米管(MWNTs)对健康小鼠生理的短期影响(最初24小时)。
通过尾静脉注射未功能化的纯化多壁纳米管(pMWNTs)和不同类型的水分散性功能化多壁纳米管(f-MWNTs)。给药后24小时收获的组织(肾脏、肝脏、脾脏和肺)的组织学检查表明,器官积聚取决于f-MWNT表面铵(NH(3)(+))功能化的程度。
MWNT-NH(3)(+)的功能化程度越高,其在组织中的积聚越少。注射前用自体血清蛋白包被的pMWNTs几乎完全以大的深色簇状积聚在肺和肝脏中。此外,血清和尿液分析的各种指标也证实,MWNT-NH(3)(+)注射在注射后最初24小时内未在所有主要器官中引起任何生理异常。有趣的是,对于用羧酸盐基团高度功能化的f-MWNTs(二乙三胺五乙酸功能化的MWNTs)或扩大到迄今为止体内注射的最高剂量(20mg/kg),也未观察到异常。
导致纳米管充分个体化的f-MWNT高度功能化而非官能团的性质是导致组织积聚减少和组织生理正常的关键因素,至少在给药后的最初24小时内如此,即使是在当今任何研究中给予的最高碳纳米管剂量下。