The Genetic and Epigenetic Toxicity of Silica Nanoparticles: An Updated Review

Manjia Zheng,1 Ziwei Chen,1 Jiling Xie,1 Qiyuan Yang,1 Minhua Mo,1 Jia Liu,2 Liangjiao Chen1 1Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jia Liu, Stomatological Hospital, Southern Medical University, No. 366 jiangnan Road South, Guangzhou, Guangdong, 510280, People’s Republic of China, Email liujia1988@smu.edu.cn Liangjiao Chen, Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, No. 31 huangsha Road, Guangzhou, Guangdong, 510145, People’s Republic of China, Email 2010686017@gzhmu.edu.cnAbstract: Silica nanoparticles (SiNPs) are widely used in biomedical fields, such as drug delivery, disease diagnosis, and molecular imaging. An increasing number of consumer products containing SiNPs are being used without supervision, and the toxicity of SiNPs to the human body is becoming a major problem. SiNPs contact the human body in various ways and cause damage to the structure and function of genetic material, potentially leading to carcinogenesis, teratogenicity and infertility. This review summarizes SiNPs-induced genetic and epigenetic toxicity, especially to germ cells, and explore their potential mechanisms. SiNPs cause genetic material damage mainly by inducing oxidative stress. Furtherly, the molecular mechanisms of epigenetic toxicity are discussed in detail for the first time. SiNPs alter DNA methylation, miRNA expression, histone modification and inhibit chromatin remodeling by regulating epigenetic-related enzymes and transcription factors. This review is beneficial for investigating potential solutions to avoid toxicity and provide guidance for better application of SiNPs in the biomedical field.Keywords: silica nanoparticles, genotoxicity, epigenetic, DNA damage, germ cells