Immunological impact of graphene oxide sheets in the abdominal cavity is governed by surface reactivity.
Immunological impact of graphene oxide sheets in the abdominal cavity is governed by surface reactivity.
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DOI：
10.1007/s00204-018-2303-z
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发表时间：
2018-11
影响因子：
6.1
通讯作者：
Bussy C
中科院分区：
文献类型：
--
作者：
Rodrigues AF;Newman L;Jasim DA;Vacchi IA;Ménard-Moyon C;Crica LE;Bianco A;Kostarelos K;Bussy C
氧化石墨烯（GO）是石墨烯的氧化形式，其在多种应用中引起了商业兴趣，包括油墨、印刷电子和喷涂，由于可能产生可吸入气溶胶，这些应用都引起了健康问题。尽管许多研究已经讨论了GO片的毒性，但其横向尺寸的体内影响仍然不清楚。在这里，我们比较了大GO片（l-GO，1-20 µm）与小GO片（s-GO，< 1 µm）在腹膜内（i. p.）小鼠注射。为了对结果进行基准测试，还测试了长而刚性的多壁碳纳米管（MWCNT），这些碳纳米管被证明与间皮上的石棉样致病性相关。我们的目的是评估横向尺寸是否可以以与MWCNT的长度类似的方式成为GO片材的致炎性的预测因子。虽然分散在0.5%BSA中的长MWCNT诱导了对肉芽肿间皮的肉芽肿反应和对腹膜腔的免疫细胞募集，但在类似条件下分散的GO片不引起任何反应，无论其横向尺寸如何。我们进一步询问通过测试不同的分散体（5%右旋糖代替0.5%BSA）来调节GO的表面反应性是否可以改变生物学结果。虽然分散的变化并没有改变GO对间皮的影响（即没有肉芽肿），我们观察到，当分散在无蛋白质的5%葡萄糖溶液中时，s-GO比l-GO或当分散在含蛋白质的溶液中时引起更多的单核细胞向腹膜腔的募集。这种募集与s-GO在体内与腹膜巨噬细胞相互作用的更大能力相一致，并且与比I-GO更大的表面反应性相关。总之，大尺寸不是腹膜内施用后GO片的免疫学影响的决定因素。对于相等的剂量，具有与长MWCNT的长度类似的横向尺寸的GO片比MWCNT的致病性更低。另一方面，表面反应性和一些较小的GO片更容易与免疫细胞相互作用的能力似乎是可以调整以改善GO安全性的关键参数。特别是，分散模式的选择，影响这两个参数，被认为是至关重要的GO在这个模型中的影响评估。总的来说，这些发现对于更好地了解GO毒性和炎症的参数以及合理设计用于各种应用（包括生物医学）的安全GO制剂至关重要。本文的在线版本（10.1007/s 00204 -018-2303-z）包含补充材料，可供授权用户使用。
Graphene oxide (GO) is an oxidised form of graphene that has attracted commercial interest in multiple applications, including inks, printed electronics and spray coatings, which all raise health concerns due to potential creation of inhalable aerosols. Although a number of studies have discussed the toxicity of GO sheets, the in vivo impact of their lateral dimensions is still not clear. Here, we compared the effects of large GO sheets (l-GO, 1–20 µm) with those of small GO sheets (s-GO, < 1 µm) in terms of mesothelial damage and peritoneal inflammation, after intraperitoneal (i.p.) injection in mice. To benchmark the outcomes, long and rigid multi-walled carbon nanotubes (MWCNTs) that were shown to be associated with asbestos-like pathogenicity on the mesothelium were also tested. Our aim was to assess whether lateral dimensions can be a predictor of inflammogenicity for GO sheets in a similar fashion as length is for MWCNTs. While long MWCNTs dispersed in 0.5% BSA induced a granulomatous response on the diaphragmatic mesothelium and immune cell recruitment to the peritoneal cavity, GO sheets dispersed under similar conditions did not cause any response, regardless of their lateral dimensions. We further interrogated whether tuning the surface reactivity of GO by testing different dispersions (5% dextrose instead of 0.5% BSA) may change the biological outcome. Although the change of dispersion did not alter the impact of GO on the mesothelium (i.e. no granuloma), we observed that, when dispersed in protein-free 5% dextrose solution, s-GO elicited a greater recruitment of monocytic cells to the peritoneal cavity than l-GO, or when dispersed in protein-containing solution. Such recruitment coincided with the greater ability of s-GO to interact in vivo with peritoneal macrophages and was associated with a greater surface reactivity in comparison to l-GO. In conclusion, large dimension was not a determining factor of the immunological impact of GO sheets after i.p. administration. For an equal dose, GO sheets with lateral dimensions similar to the length of long MWCNTs were less pathogenic than the MWCNTs. On the other hand, surface reactivity and the ability of some smaller GO sheets to interact more readily with immune cells seem to be key parameters that can be tuned to improve the safety profile of GO. In particular, the choice of dispersion modality, which affected these two parameters, was found to be of crucial importance in the assessment of GO impact in this model. Overall, these findings are essential for a better understanding of the parameters governing GO toxicity and inflammation, and the rational design of safe GO-based formulations for various applications, including biomedicine. The online version of this article (10.1007/s00204-018-2303-z) contains supplementary material, which is available to authorized users.
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