Abstract
Carbon nanomaterials, including 2D graphene-based materials, have shown promising applicability to drug delivery, tissue engineering, diagnostics, and various other biomedical areas. However, to exploit the benefits of these materials in some of the areas mentioned, it is necessary to understand their possible toxicological implications and long-term fate in vivo. We previously demonstrated that following intravenous administration, 2D graphene oxide (GO) nanosheets were largely excreted via the kidneys; however, a small but significant portion of the material was sequestered in the spleen. Herein, we interrogate the potential consequences of this accumulation and the fate of the spleen-residing GO over a period of nine months. We show that our thoroughly characterized GO materials are not associated with any detectable pathological consequences in the spleen. Using confocal Raman mapping of tissue sections, we determine the sub-organ biodistribution of GO at various time points after administration. The cells largely responsible for taking up the material are confirmed using immunohistochemistry coupled with Raman spectroscopy, and transmission electron microscopy (TEM). This combination of techniques identified cells of the splenic marginal zone as the main site of GO bioaccumulation. In addition, through analyses using both bright-field TEM coupled with electron diffraction and Raman spectroscopy, we reveal direct evidence of in vivo intracellular biodegradation of GO sheets with ultrastructural precision. This work offers critical information about biological processing and degradation of thin GO sheets by normal mammalian tissue, indicating that further development and exploitation of GO in biomedicine would be possible.
Highlights
Carbon nanomaterials, including 2D graphenebased materials, have shown promising applicability to drug delivery, tissue engineering, diagnostics, and various other biomedical areas
In terms of physicochemical characteristics, we showed that thicker Graphene-based materials (GBMs) such as multilayer graphene oxide (GO) sheets are more likely to be trapped within the capillary beds of the lungs compared with single-to-few-layer GO sheets, after systemic administration.[12]
Using confocal Raman mapping, as well as immunohistochemistry and conventional Raman spectroscopy in combination, to map the splenic distribution of GO, we identified that a subpopulation of splenic macrophages, known as the marginal zone macrophages, were the predominant cells responsible for bioaccumulating the material
Summary
Carbon nanomaterials, including 2D graphenebased materials, have shown promising applicability to drug delivery, tissue engineering, diagnostics, and various other biomedical areas. The cells largely responsible for taking up the material are confirmed using immunohistochemistry coupled with Raman spectroscopy, and transmission electron microscopy (TEM) This combination of techniques identified cells of the splenic marginal zone as the main site of GO bioaccumulation. Graphene-based materials (GBMs) have potential for exciting applications including those related to medical technologies, such as improved drug delivery.[1−4] A key concern, is the implications of interactions of these engineered nanomaterials with the mammalian biological milieu.[5] Understanding the fate of GBMs after administration to the body and the materials’ tendencies to accumulate within organs and cells, especially those of the mononuclear phagocytic system (MPS), such as the lungs, liver and spleen, and the effects thereof,[6,7] are key in defining whether GBMs will be suitable for biomedical applications. One aspect that is sensitive to variations in physicochemical characteristics is the in vivo long-term fate and, in particular, the biodegradability of the materials.[5,17,18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
