Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Abstract

Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. This study describes adverse effects of GO and amino‐functionalized GO (GONH2) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA‐Sequencing data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK‐1, which is a well‐established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk‐1 mutants show reduced tissue‐functionality and facultative vivipary. In a direct comparison, GONH2 exposure does not cause detrimental effects in the wild type or in pmk‐1 mutants, and the innate immune response is considerably less pronounced. This work establishes enhanced biocompatibility of amino‐functionalized GO in a whole‐organism, emphasizing its potential as a biomedical nanomaterial.

Toxicity of Low-dose Graphene Oxide Nanoparticles in an in-vivo Wild Type of Caenorhabditis elegans Model

“…The results showed that higher concentrations of GO NPs induced more reproductive toxicity based on our experiments on brood size number in nematodes. Our results were consistent with most GO NP studies reporting that GO exposure can cause adverse effects through damaging the fertility and egg ejection behavior of nematodes (Kim et al, 2018;Rive et al, 2019, Wu et al, 2013Zhao et al, 2016b). Wu et al (2013) showed that C. elegans with prolonged exposure to 1-100 mg L -1 exhibited significantly decreased brood size compared to the control, but there were no significant between-group differences at 0.1 and 0.5 mg L -1 .…”

“…Kim et al (2018) revealed that accumulation of GO NPs (10 mg L -1 ) in the reproductive organs, which might be the direct cause of reproductive toxicity, could reduce brood size and sperm count by suppressing spermatogenesis of the hermaphrodite nematodes at the GO levels of 5 or 10 mg L -1 . However, the negative impact of GO NP exposure on the reproductive function in the present and published studies (Kim et al, 2018;Rive et al, 2019, Wu et al, 2013Zhao et al, 2016b), as well as our results, suggest that prolonged exposure to GO NPs at low doses from 0.0100 to 1.00 g L -1 could decrease progeny number or fecundity in N2 C elegans models.…”

“…elegans is considered to be a novel tool for in-vivo techniques, and testing of C. elegans is known to be analogous to mammalian neurotoxin testing (Cole et al, 2004). Recently, scientists have focused on the disruption of biological effects from ROS, reproductive effects, gene expression, neurological development, and neurobehavior with treatment of GO NPs in C. elegans models (Kim et al, 2018;Kim et al, 2020;Qu et al, 2017;Rive et al, 2019;Wu et al, 2013;Zhao et al, 2020). Zhang et al (2012) indicated no negative impact on longevity after exposing L4-larva-toyoung-adult C. elegans to GO NPs at concentrations ranging from 5 to 20 mg L -1 .…”

“…Liu et al (2020) observed that GO NPs induced intestinal barrier dysfunction in C. elegans. Rive et al (2019) proposed that worms chronically (or prolongedly) exposed to GO NPs (levels of 100 and 200 mg L -1 ) were significantly shortened in size and developed morphological abnormalities in the pharynx and intestine. Kim et al (2018) found accumulation of GO NPs in the reproductive organs of C.…”

Toward High‐Dimensional Single‐Cell Analysis of Graphene Oxide Biological Impact: Tracking on Immune Cells by Single‐Cell Mass Cytometry

“…[ 38 ] Some of the chemical properties include large surface area, diverse functionalities, and good biocompatibility. [ 8,39,40 ] These properties of GO allow it to be studied for several applications in nanomedicine, including bioimaging, biosensing and tissue regeneration. [ 41,42 ] However, the increasing use and large‐scale production of this material also necessitates careful investigations of its impact on human tissues.…”