Confocal Raman Imaging Study Showing Macrophage Mediated Biodegradation of Graphene In Vivo

Abstract

This study is focused on the crucial issue of biodegradability of graphene under in vivo conditions. Characteristic Raman signatures of graphene are used to three dimensionally (3D) image its localization in lung, liver, kidney and spleen of mouse and identified gradual development of structural disorder, happening over a period of 3 months, as indicated by the formation of defect-related D'band, line broadening of D and G bands, increase in ID /IG ratio and overall intensity reduction. Prior to injection, the carboxyl functionalized graphene of lateral size ∼200 nm is well dispersed in aqueous medium, but 24 hours post injection, larger aggregates of size up to 10 μm are detected in various organs. Using Raman cluster imaging method, temporal development of disorder is detected from day 8 onwards, which begins from the edges and grows inwards over a period of 3 months. The biodegradation is found prominent in graphene phagocytosed by tissue-bound macrophages and the gene expression studies of pro-inflammatory cytokines indicated the possibility of phagocytic immune response. In addition, in vitro studies conducted on macrophage cell lines also show development of structural disorder in the engulfed graphene, reiterating the role of macrophages in biodegradation. This is the first report providing clear evidence of in vivo biodegradation of graphene and these results may radically change the perspective on potential biomedical applications of graphene.

Three‐Dimensional Graphene: A Biocompatible and Biodegradable Scaffold with Enhanced Oxygenation

“…Both of these observations (i.e., the changes in G-peak and D-peak) are different to what is observed in 2D-graphene on the nanoscale. [ 19 ] This dissimilarity arises from the difference in scale of the sp 2 C-C network: for 2D-graphene in the nano regime, which is mostly monolayer, the changes in the Raman signatures during biodegradation process are mainly caused by the changes in size of the 2D-fl akes in the lateral directions, such as the breaking of the sp 2 C-C network and the reduction of the distance between the defects that causes variation to the phonons' vibration mode. For 3D-C, considering the entire structure as a whole, the Raman signatures are dominated by the superposition of a stack of graphene (i.e., the bulk form).…”

“…For the O 2 -plasma case, fl akes were fi rst decomposed into Raman spectroscopy of this similarity is described in Supporting Information, Figure S5). [ 19,41 ] Since this biodegradation experiment was carried out at 4°C, the biodegradation of the bulk foams was slowed down relative to that at physiological temperatures. To demonstrate more clearly the effects on 3D-C, a second biodegradation test was carried out at room temperature (which speeded up the process signifi cantly).…”

“…[ 19 ] In addition, the speed of biodegradation can be tuned by pretreatment with O 2 plasma, which also enhances the wettability of the scaffold, as stated in the preparation method for cell culture. Similarly, if the process has to be slowed down, a different pretreatment can be carried out to remove the intrinsically formed -OH groups from the foam (induced through the postannealing step after etching).…”

“…It is also crucial that the rate at which degradation occurs coincides as much as possible with the rate of tissue formation. [ 17 ] So far, most of the biodegradation studies for carbon-based materials are on the nanoscale, such as graphene [ 19 ] and carbon nanotubes (CNTs). [ 26 ] The degradation process from macroscopic to microscopic scale has not been studied.…”

Graphene Oxide/Ag Nanoparticles Cooperated with Simvastatin as a High Sensitive X‐Ray Computed Tomography Imaging Agent for Diagnosis of Renal Dysfunctions

“…Moreover, the multifunctional GO and its composites have been synthesized for in vivo imaging of GO through Raman, fluorescence, radioactive, and infrared imaging technology, and so on. [16][17][18][19][20][21] Importantly, in vivo CT imaging of GO to tumor also has been preliminarily studied by labeling of metal nanoparticles. [22][23][24][25] Shi et al [22] synthesized the GO@Ag-DOX nanoparticles for chemo-photothermal therapy and X-ray imaging of the subcutaneous tumor.…”