Reversing the systemic biotoxicity of nanomaterials by downregulating ROS-related signaling pathways in the multi-organs of Zebrafish embryos

• Published in: Materials chemistry frontiers 2021-06, Vol.5 (11), p.4231-4243
• Main Authors: Zheng, Bin, Guo, Mingming, Song, Xin, Miao, Yaodong, Pang, Meijun, Ming, Dong
• Format: Article
• Language: English
• Subjects: Antioxidants; Apoptosis; Biocompatibility; Biomedical materials; Blood vessels; Cadmium selenide; Cadmium selenides; Camouflage; Cardiovascular system; Core-shell structure; Embryos; Genetic modification; Glutathione; Immune system; Medical imaging; Molecular structure; Nanomaterials; Nerves; Nervous system; Organic chemistry; Organs; Peroxidase; Polyethylene glycol; Quantum dots; Silicon dioxide; Superoxide dismutase; Toxicity
• ISSN: 2052-1537; 2052-1537
• DOI: 10.1039/d1qm00193k

Nanomaterials have broad application prospects in human health and diseases, including medical imaging and drug delivery and treatment. With the gradual advent of the nano era, the safety of nanomaterials in biology and the environment must be evaluated more widely and deeply. Herein, we scanned some widely used biomedical nanomaterials toxicity with an in vivo zebrafish model and demonstrated that cadmium selenide (CdSe) quantum dots (QDs) were the most toxic. Embryos exposed to CdSe QDs showed the activation of NADPH oxidase nox4 and an excessive generation of reactive oxygen species (ROS). The expression of antioxidant defense enzyme superoxide dismutase sod1 and glutathione peroxidase gpx1 increased the response to oxidative stress. Further, excessive ROS activated apoptosis by the p53 - and caspase-3 -mediated signaling pathway. Several modification methods, including silica coating, core-shell structure development, and organic molecular camouflage were applied to reduce the toxicity of the materials, whereby the polyethylene glycol (PEG) camouflage method exhibited better performance for improving the biocompatibility of CdSe QDs, which could effectively reduce ROS and apoptosis induced by CdSe QDs in the zebrafish model. Meanwhile, we employed a series of genetically modified zebrafish models to assess the CdSe QDs toxicity, and the polyethylene glycol (PEG) camouflage showed protective effects in the heart, nerves, blood vessels, and immune system. CdSe QDs disguised by PEG could effectively alleviate the toxicity of CdSe QDs in multiple organs. In summary, our data revealed that CdSe QDs induced an excessive production of ROS, which would activate the apoptosis pathway mediated by p53 and caspase-3 and resulted in cardiovascular system, nervous system, and immune system toxicity. PEG camouflage could effectively decrease ROS generation and apoptosis to improve the biocompatibility of CdSe QDs. PEG camouflaged CdSe QDs can effectively reduce the multi-organs toxicity of CdSe QDs by nox4-ROS-p53-caspase-3 mediated apoptosis signaling pathway.