Abstract
The incorporation of functional groups endows graphene oxide (GO) with different surface charges, which plays important roles in biological interactions with cells. However, the effect of surface charge of GO derivatives on ocular biocompatibility has not been fully elucidated. Previously, we found that positively, negatively and neutrally charged PEGylated GO (PEG-GO) nanosheets exerted similar effect on the viability of ocular cells. In this work, we performed in vitro and in vivo studies to comprehensively study the effect of surface charge of PEG-GO on ocular compatibility. The in vitro results showed that the cellular uptake efficacy of negatively charged PEG-GO nanosheets was significantly decreased compared with positively charged and neutrally charged analogs. However, three kinds of PEG-GO nanosheets produced similar amounts of intracellular reactive oxygen species and showed similar influence on mitochondrial membrane potential. By analysis of global gene expression profiles, we found that the correlation coefficients between three kinds of PEG-GO-treated cells were more than 0.98. Furthermore, in vivo results showed that all these PEG-GO nanosheets had no significant toxicity to ocular structure and function. Taken together, our work suggested that surface charge of PEG-GO exerted negligible effect on its ocular compatibility, except for the cellular uptake. Our work is conducive to understanding the relationship between surface charge and biocompatibility of GO derivatives.
Highlights
Graphene-based nanomaterials have promoted advancements in biomedical fields due to their unique nanoscopic properties and tunable multiple functions [1,2,3]
PEG-graphene oxide (GO) nanosheets with different surface charges were prepared according to our previous study, that is GO-PEG-NH2, GO-PEG-COOH and GO-PEG-OCH3 with positive, negative and neutral surface charges, respectively [22]
Atomic force microscopy images showed that the lateral size of PEGylated GO (PEG-GO) samples was about 65 nm, and the thickness was about 2 nm
Summary
Graphene-based nanomaterials have promoted advancements in biomedical fields due to their unique nanoscopic properties and tunable multiple functions [1,2,3]. Graphene oxide (GO) and its derivatives exhibit infinite potential for drug delivery applications [2,3,4,5,6]. In order to improve the efficiency of drug delivery, as a drug platform, GO is usually incorporated by different reactive groups [1,3,6]. The incorporation of functional groups endows GO with different surface charges, which can influence the cellular uptake and drug delivery efficiency [7,8,9,10]. The effect of surface charge of GO derivatives on nanotoxicology remains controversial so far. Tu et al found that the positively charged reduced GO nanosheets possessed higher cellular uptake efficiency, as well as higher cytotoxicity, than negatively and neutrally
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