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. 2021 Jun 3;8(1):44.
doi: 10.1186/s40643-021-00400-7.

In vivo toxicity and antitumor activity of newly green synthesized reduced graphene oxide/silver nanocomposites

Mohamed M El-Zahed  1 , Zakaria A Baka  2 , Mohamed I Abou-Dobara  2 , Ahmed K El-Sayed  2 , Magy M Aboser  3 , Ayman Hyder  4
Affiliations

In vivo toxicity and antitumor activity of newly green synthesized reduced graphene oxide/silver nanocomposites

Mohamed M El-Zahed et al. Bioresour Bioprocess. .

Abstract

A novel biosynthesis of dual reduced graphene oxide/silver nanocomposites (rGO/AgNC) using the crude metabolite of Escherichia coli D8 (MF06257) strain and sunlight is introduced in this work. Physicochemical analysis of these rGO/AgNC revealed that they are sheet-like structures having spherically shaped silver nanoparticles (AgNPs) with an average particle size of 8 to 17 nm, and their absorption peak ranged from 350 to 450 nm. The biosynthesized rGO/AgNC were characterized by UV-vis and FT-IR spectra, X-ray diffraction, Zeta potential and transmission electron microscopy. After the injection of these nanocomposites to mice, their uptake by the kidney and liver has been proven by the ultrastructural observation and estimation of the hepatic and renal silver content. These nanocomposites caused a moderate toxicity for both organs. Changes in the liver and kidney functions and histopathological effects had been observed. The rGO/AgNC revealed a remarkable antitumor effect. They showed a dose-dependent cytotoxic effect on Ehrlich ascites carcinoma (EAC) cells in vitro. Treatment of mice bearing EAC tumors intraperitoneally with 10 mg/kg rGO/AgNC showed an antiproliferative effect on EAC cells, reduced ascites volume, and maintained mice survival. The results indicate that this green synergy of silver nanoparticles with reduced graphene oxide may have a promising potential in cancer therapy.

Keywords: Antitumor; Ehrlich ascites carcinoma; In vivo toxicity; Nanocomposites; Reduced graphene oxide; Silver nanoparticles.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Characterization of reduced graphene oxide (GO)/silver nanocomposites (AgNC) biosynthesized by metabolite of E. coli. A The UV–vis spectra of GO and rGO/AgNC. B FT-IR spectra of GO and rGO/AgNC. C The X-ray diffraction (XRD) patterns of the GO and rGO. D The XRD patterns of rGO/AgNC. E Zeta potential measurement analysis of rGO/AgNC. F Transmission electron microscopy (TEM) of GO. G TEM of rGO/AgNC
Fig. 2
Fig. 2
The stability and releasability of reduced graphene oxide (GO)/silver nanocomposites (AgNC) biosynthesized by metabolite of E. coli: A The UV–vis spectra of rGO/AgNC at both zero time and after storage for 7 days in dark or light conditions. B The release property of AgNO3 vs. AgNPs from rGO/AgNC at 37 °C
Fig. 3
Fig. 3
Effect of rGO/Ag nanocomposite biosynthesized by E. coli on mice liver. A silver content in the hepatic tissue. B TEM of control hepatocytes showing nuclei (N) and mitochondria (M). C TEM of hepatocytes from mice treated with rGO/AgNC showing cytoplasmic vacuolation (V) associated with the presence of silver nanoparticles (NP). Liver function was assessed by assessing serum ALT (D), AST (E) and albumin (Fig. 6D). Histopathologic effect in livers of mice treated with rGO/AgNC (G), compared to the control livers (F). Abbreviations: PV, portal vein; CV, central vein; straight arrows show mild inflammatory leucocyte infiltration; curved arrows show areas of pycnotic nuclei and focal necrosis. * denotes statistically significant different value from the control one (t-test)
Fig. 4
Fig. 4
Reduced GO/Ag nanocomposites biosynthesized by E. coli are largely taken up by the kidney. TEM of convoluted tubules epithelia A, control; B and C, nanocomposite-treated) showing shrinking nuclei (N), mitochondrial aberration (M) and thickened basement membranes (arrows) in B and C, compared to that in A. D silver content in the renal tissue. E Nanocomposite treatment increases serum creatinine. The * in D and E denotes statistically significant different value from the control one (unpaired t-test). Histopathologic effect in kidneys of mice treated with rGO/AgNC (G), compared to the control (F), show dilated Bowman space of the renal corpuscles (RC) and degenerated and necrotic tubular epithelia (arrows)
Fig. 5
Fig. 5
In vitro toxicity of rGO/AgNC in Ehrlich ascites carcinoma cells. Cells were incubated with different concentrations of the nanocomposite for 1 h and viability was determined by trypan blue. * denotes significantly different values from the control one (ANOVA p < 0.05)
Fig. 6
Fig. 6
Antitumor effect of rGO/AgNC in vivo. A Daily reductions in Ehrlich ascites carcinoma (EAC) cells in the peritoneal exudate of mice treated with 10 mg/kg rGO/AgNC for 7 days, a week after initial 4 × 106 EAC cell injection. B–D The nanocomposite reduces the ascites volume in EAC-bearing mice: B control mice, C mice injected initially with EAC cells, and D EAC-bearing mice treated daily with rGO/AgNC. E, F Restoration of the body weight and abdominal circumference in EAC-bearing mice after rGO/AgNC treatment. G Treatment with rGO/AgNC restores serum albumin level (ANOVA p < 0.05, * and # denote significantly different values, as determined by post hoc t-test, from the control and EAC-bearing group, respectively)
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