Synthesis, Characterization, and Toxicity Assessment of Pluronic F127-Functionalized Graphene Oxide on the Embryonic Development of Zebrafish (Danio rerio)

Int J Nanomedicine. 2020 Oct 28:15:8311-8329. doi: 10.2147/IJN.S271159. eCollection 2020.

Abstract

Background: In the current literature, there are ongoing debates on the toxicity of graphene oxide (GO) that demonstrate contradictory findings regarding its toxicity profile. As a potential drug carrier, these findings are very concerning due to the safety concerns in humans, as well as the dramatic rise of GO being excreted into the environment. Therefore, there is an imperative need to mitigate the potential toxicity of GO to allow for a safer application in the future.

Purpose: The present study aims to address this issue by functionalizing GO with Pluronic F127 (PF) as a means to mitigate toxicity and resolve the biocompatibility of GO. Although results from previous studies generally indicated that Pluronic functionalized GO exhibits relatively low toxicity to living organisms, reports that emphasize on its toxicity, particularly during embryonic developmental stage, are still scarce.

Methods: In the present study, two different sizes of native GO samples, GO and NanoGO, as well as PF-functionalized GO, GO-PF and NanoGO-PF, were prepared and characterized using DLS, UV-Vis, Raman spectroscopy, FTIR, and FESEM analyses. Toxicological assessment of all GO samples (0-100 µg/mL) on zebrafish embryonic developmental stages (survival, hatching and heart rates, and morphological changes) was recorded daily for up to 96 hours post-fertilization (hpf).

Results: The toxicity effects of each GO sample were observed to be higher at increasing concentrations and upon prolonged exposure. NanoGO demonstrated lower toxicity effects compared to GO. GO-PF and NanoGO-PF were also found to have lower toxicity effects compared to native GO samples. GO-PF showed the lowest toxicity response on zebrafish embryo.

Conclusion: These findings highlight that toxicity is dependent on the concentration, size, and exposure period of GO. Functionalization of GO with PF through surface coating could potentially mitigate the toxicity effects of GO in embryonic developmental stages, but further investigation is warranted for broader future applications.

Keywords: embryogenesis; graphene oxide; nanomaterial; pluronic; toxicity.

MeSH terms

  • Animals
  • Embryo, Nonmammalian / drug effects
  • Graphite / chemical synthesis
  • Graphite / chemistry*
  • Graphite / toxicity*
  • Nanostructures / chemistry
  • Nanostructures / toxicity*
  • Poloxamer / chemistry
  • Poloxamer / toxicity*
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • Spectrum Analysis, Raman
  • Toxicity Tests
  • Zebrafish / embryology*

Substances

  • graphene oxide
  • Poloxamer
  • Graphite

Grants and funding

This research was funded by research grants from Ministry of Higher Education of Malaysia, namely Fundamental Research Grant Scheme (FRGS), grant number 04-01-18-1931FR and Universiti Putra Malaysia (GP/IPM/2016/9513200). Authors acknowledge the facilities, scientific and technical assistance from the Institute of Advanced Technology (ITMA) and Institute of Biosciences (IBS) at Universiti Putra Malaysia.