Splenic Capture and In Vivo Intracellular Biodegradation of Biological-Grade Graphene Oxide Sheets

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.

Respiratory and systemic impacts following MWCNT inhalation in B6C3F1/N mice

“…These observations suggest that potential distal effects of "benign" MWCNT were potentially mediated by the immune system, wherein local macrophages trafficked the particles through normal immune pathways. Additionally, while studies evaluating splenic deposition of nanoparticles [26,27], noted particles introduced intravenously or intraperitoneally were found in the red pulp regions, the present studies suggest deposition in the white pulp areas with resulting immune effects of population changes and apoptosis. The end result of this particle translocation was terminal deposition in the spleen resulting in more substantial chronic effects.…”

Large‐Sized Graphene Oxide Nanosheets Increase DC–T‐Cell Synaptic Contact and the Efficacy of DC Vaccines against SARS‐CoV‐2

“…This means that <1.0 µg of GO was subcutaneously injected per mouse, which was three orders of magnitude lower than the well‐tolerated dose in vivo according to a previous report. [ 31 ] In addition, the route of subcutaneous delivery can avoid the direct entry of GOs into the systemic circulation, greatly reducing potential hazards. A complete blood cell count (Table S2 , Supporting Information) one week after the last DC vaccination revealed no statistically significant differences from values obtained for untreated mice.…”

In Situ Formation of 3D Conductive and Cell‐Laden Graphene Hydrogel for Electrically Regulating Cellular Behavior

“…PVA has excellent biocompatibility and safety with FDA approval for clinical uses in humans. A very recent study [ 49 ] also demonstrated an encouraging result of in vivo biodegradation of GO which makes the GO based hydrogel promising in biomedical applications.…”