J Biomed Nanotechnol. 2021 Jan 1;17(1):131-148. doi: 10.1166/jbn.2021.3006.
Graphene, including graphene quantum dots, its oxide and unoxidized forms (pure graphene) have several properties, like fluorescence, electrical conductivity, theoretical surface area, low toxicity, and high biocompatibility. In this study, we evaluated genotoxicity ( analysis using the functional density theory-FDT), cytotoxicity (human glioblastoma cell line), pharmacokinetics, impact on microcirculation and cell internalization assay. It was also radiolabeled with lutetium 177 (177Lu), a beta emitter radioisotope to explore its therapeutic use as nanodrug. Finally, the impact of its disposal in the environment was analyzed using ecotoxicological evaluation. FDT analysis demonstrated that graphene can construct covalent and non-covalent bonds with different nucleobases, and graphene oxide is responsible for generation of reactive oxygen species (ROS), corroborating its genotoxicity. On the other hand, non-cytotoxic effect on glioblastoma cells could be demonstrated. The pharmacokinetics analysis showed high plasmatic concentration and clearance. Topical application of 0.1 and 1 mg/kg of graphene nanoparticles on the hamster skinfold preparation did not show inflammatory effect. The cell internalization assay showed that 1-hour post contact with cells, graphene can cross the plasmatic membrane and accumulate in the cytoplasm. Radio labeling with 177Lu is possible and its use as therapeutic nanosystem is viable. Finally, the ecotoxicity analysis showed that exposed to graphene showed pronounced uptake and absorption in the nauplii gut and formation of ROS. The data obtained showed that although being formed exclusively of carbon and carbon-oxygen, graphene and graphene oxide respectively generate somewhat contradictory results and more studies should be performed to certify the safety use of this nanoplatform.
石墨烯,包括石墨烯量子点、其氧化物和未氧化形式(纯石墨烯),具有多种性质,如荧光性、导电性、理论表面积、低毒性和高生物相容性。在这项研究中,我们评估了遗传毒性(使用功能密度理论-FDT 分析)、细胞毒性(人神经胶质瘤细胞系)、药代动力学、对微循环的影响和细胞内化试验。它还被放射性标记为镥 177(177Lu),一种β发射放射性同位素,以探索其作为纳米药物的治疗用途。最后,使用生态毒理学评价分析了其在环境中的处置影响。FDT 分析表明,石墨烯可以与不同的碱基形成共价和非共价键,而石墨烯氧化物是产生活性氧物种(ROS)的原因,证实了其遗传毒性。另一方面,对神经胶质瘤细胞没有表现出非细胞毒性作用。药代动力学分析显示其在血浆中有高浓度和清除率。在仓鼠皮肤皱褶制剂上应用 0.1 和 1 mg/kg 的石墨烯纳米粒子的局部应用没有显示出炎症作用。细胞内化试验表明,与细胞接触 1 小时后,石墨烯可以穿过质膜并在细胞质中积累。用 177Lu 进行放射性标记是可能的,并且其作为治疗性纳米系统是可行的。最后,生态毒性分析表明,暴露于石墨烯的桡足类幼体肠道明显吸收和吸收,并形成 ROS。所获得的数据表明,尽管石墨烯和石墨烯氧化物分别仅由碳和碳-氧组成,但它们分别产生了有些矛盾的结果,需要进行更多的研究以证明这种纳米平台的安全使用。