<p>The NLRP3-Mediated Neuroinflammatory Responses to CdTe Quantum Dots and the Protection of ZnS Shell</p>

Abstract

Introduction: Since CdTe quantum dots (QDs) are still widely considered as advanced fluorescent probes because of their far superior optical performance and fluorescence efficiency over non-cadmium QDs, it is important to find ways to control their toxicity. Methods: In this study, the adverse effects of two cadmium-containing QDs, ie, CdTe QDs and CdTe@ZnS QDs, on the nervous system of nematode C. elegans, the hippocampus of mice, and cultured microglia were measured in order to evaluate the neuroinflammation caused by cadmium-containing QDs and the potential mechanisms. Results: Firstly, we observed that cadmium-containing QD exposure-induced immune responses and neurobehavioral deficit in nematode C. elegans. In the mice treated with QDs, neuroinflammatory responses to QDs in the hippocampus, including microglial activation and IL-1ß release, occurred as well. When investigating the mechanisms of cadmium-containing QDs causing IL-1ß-mediated inflammation, the findings suggested that cadmium-containing QDs activated the NLRP3 inflammasome by causing excessive ROS generation, and resulted in IL-1ß release. Discussion: Even though the milder immune responses and neurotoxicity of CdTe@ZnS QDs compared with CdTe QDs indicated the protective role of ZnS coating, the inhibitions of NLRP3 expression and ROS production completely reduced the IL-1ß-mediated inflammation. This provided valuable information that inhibiting target molecules is an effective and efficient way to alleviate the toxicity of cadmium-containing QDs, so it is important to evaluate QDs through a mechanism-based risk assessment.

Neurotoxicity Evaluation of Nanomaterials Using C. elegans: Survival, Locomotion Behaviors, and Oxidative Stress

“…Similarly, impairments of various neurons (e.g., AFD sensory neurons, RME motor neurons, and dopaminergic neurons) have been observed in response to graphene‐based nanomaterials, silver nanoparticles, copper oxide nanoparticles, and cadmium telluride quantum dots (Kim et al., 2020; Mashock et al., 2016; Piechulek & von Mikecz, 2018; Zhao, Wang, Wu, Li, & Wang, 2015). In addition, behavioral defects, including alterations to body bending, head thrashing, pharyngeal pumping, and defecation intervals, have been reported upon exposure to graphene‐based nanomaterials, cadmium telluride quantum dots, and TiO 2 , silica, and polystyrene nanoparticles (Kim et al., 2020; Scharf, Gührs, & von Mikecz, 2016; Shang et al., 2021; T. Wu, Liang, et al., 2020). Last but not least, nanomaterials such as silica, silver, or other airborne nanoparticles can induce neurodegenerative damage, such as β amyloid formation and protein aggregation (Piechulek & von Mikecz, 2018; Scharf et al., 2016; von Mikecz & Schikowski, 2020).…”

Immunomodulation, Toxicity, and Therapeutic Potential of Nanoparticles

“…In the exposed mice, CdS quantum dots altered the phagocytic activity of macrophages [ 64 ]. Recently, CdS quantum dots exposure was shown to enhance neuroinflammatory response via activation of NLRP3 in the exposed C. elegans, mice, and microglia cells [ 65 ]. Interestingly, the immunogenic responses evoked by the CdS quantum dots were rescued upon their modification achieved through ZnS conjugation.…”

New insights into the safety assessment of quantum dots: potential release pathways, environmental transformations, and health risks

“…199 The remaining QDs enter the body fluid circulation with the flow of fluid bodies, targeting the distribution and accumulation in different tissues and organs; they can accumulate in the lungs, heart, liver, spleen, kidney, testis, and brain, 195,196,200 causing hepatotoxicity, 201–203 reproductive toxicity, 204–210 immunotoxicity, 211,212 and neurotoxicity. 213–219 The mechanism will be summarized in section 5.…”

“…302–305 CdTe QDs can trigger mitochondrial dysfunction in hepatocytes via ROS, leading to apoptosis, 306 and CdSe/ZnS QDs can lead to ROS accumulation, altered phagocytosis, and increased apoptosis in macrophages. 211 The excessive accumulation of ROS generated by QDs which can mediate not only the induction of apoptosis but also other forms of ROS-mediated cell death can also be triggered, such as autophagy, 307–312 inflammation, 201,203,216,313–316 pyroptosis, 203,214,316 necrosis, 317–319 and ferroptosis. 320…”