Vedakumari Weslen S, Prabu Periyathambi, Babu Saravana C, Sastry Thotapalli P
Bio-Products Laboratory, Central Leather Research Institute, Adyar, Chennai, India.
Biochim Biophys Acta. 2013 Aug;1830(8):4244-53. doi: 10.1016/j.bbagen.2013.04.032. Epub 2013 May 1.
Several issues have been raised emphasizing the harmful toxic effects of metal nanoparticles towards biological systems. Search of biological nanoparticles with excellent biocompatibility and bioavailability could address this problem.
Fibrin nanoparticles (FNP) were prepared using a novel technique and characterized for their physico-chemical properties. In vitro studies were performed to examine cytotoxicity and cellular uptake of FNP. Innate immune response to FNP was studied by (i) estimating in vitro generation of complement split products, C3a and C4d and (ii) in vivo expression of pro-inflammatory cytokines, TNF-α, IL-1 and IL-6. In vivo biodistribution study was carried out by intravenous administration of FITC-labelled FNP in mice.
FNP were spherical with size ranging from 25 to 28nm. In vitro studies proved the biocompatibility of the nanoparticles, with their distribution across the cytoplasm and nucleus of treated cells. Complement activation studies showed insignificant increase in the level of C3a when compared with positive control. RT-PCR results revealed significant upregulation of TNF-α and downregulation of IL-6 cytokines after 6h of FNP administration. In vivo biodistribution studies showed moderate blood circulation time, with predominant distribution of nanoparticles in the liver followed by the lungs, kidney and spleen. Haematology, serum biochemistry, and histopathology analyses demonstrated that FNP were non-toxic.
Owing to their small size, low cost, ease of preparation and excellent biocompatibility, FNP might be a promising novel material for drug delivery applications.
Our results demonstrate the safe and promising use of FNP for biomedical applications.
已经提出了几个问题，强调金属纳米颗粒对生物系统的有害毒性作用。寻找具有优异生物相容性和生物利用度的生物纳米颗粒可以解决这个问题。
使用一种新技术制备纤维蛋白纳米颗粒（FNP），并对其物理化学性质进行表征。进行体外研究以检查FNP的细胞毒性和细胞摄取。通过（i）估计补体裂解产物C3a和C4d的体外生成以及（ii）促炎细胞因子TNF-α、IL-1和IL-6的体内表达来研究对FNP的天然免疫反应。通过在小鼠中静脉注射FITC标记的FNP进行体内生物分布研究。
FNP呈球形，大小范围为25至28nm。体外研究证明了纳米颗粒的生物相容性，它们分布在处理过的细胞的细胞质和细胞核中。补体激活研究表明，与阳性对照相比，C3a水平的增加不显著。RT-PCR结果显示，给予FNP 6小时后，TNF-α显著上调，IL-6细胞因子下调。体内生物分布研究表明血液循环时间适中，纳米颗粒主要分布在肝脏，其次是肺、肾和脾。血液学、血清生化和组织病理学分析表明FNP无毒。
由于其尺寸小、成本低、易于制备和优异的生物相容性，FNP可能是一种有前途的新型药物递送应用材料。
我们的结果证明了FNP在生物医学应用中的安全和有前途的用途。
