Review Article

Toxicity of Nanoparticles in Biomedical Application: Nanotoxicology

Table 2

In vitro and in vivo studies for the genotoxic effect of NPs.

S/no.NanoparticlesIn vitro studiesIn vivo studies

1.Carbon-based NPs
Single-wall carbon nanotubes (SWCNTs)Single- and double-strand DNA lesions in Chinese hamster fibroblasts (V79 cell line) for 3 h at 96 µg/cm2 [90].Genotoxicity via inhalation exposure in mice (C57BL). Causes immediate inflammatory reaction, fibrosis, oxidative stress, and hyperplasia [100].
Multiwall carbon nanotubes (MWCNTs)Induce apoptosis in the stem cells of mouse embryo via P53 protein activation; cause DNA damage [101103].Absence of genotoxicity in rats [104, 105].
Causes DNA damage in the lung cells, bone marrow, and leucocytes of mice [106, 107].

2.Silver NPs: gained wide application in both food and medical purposes owing to its antimicrobial activity [108]The micronucleus assay and comet assay confirmed the mutagenic and genotoxic effect of AgNPs [17, 109112].Causes DNS damage in mice lung cells and testis in size-dependent toxicity [113].

3.Gold NPs: useful in gene and drug delivery as well as deep tissue imagingAuNPs on various cell lines showed chromosomal aberration, micronuclei formation, oxidative DNA damage, and strand lesions [114117].Negative genotoxic results in mice but chronic and acute intraperitoneal administration of 10 and 30 nm Au NPs induced DNA damage evaluated by comet assay in the liver, blood, and cerebral cortex cells of rats [118].

4.Titanium dioxide (TiO2) NPs: titanium dioxide (TiO2) NPs porous TiO2 [119], TiO2 nanotubes [120], and TiO2 nanocomposite [121] have been studied as smart drug delivery carriers; also approved in EU as a food additive (E171)A 20 nm TiO2 NPs induced genotoxicity in Syrian hamster embryo fibroblasts at various concentrations ranging from 0.5–10 mg/cm2 via the production of ROS as a result of the NPs interaction with the cell membrane [122]. A dose-dependent DNA lesion has been reported upon exposure of HEpG-2 cell to a range of TiO2 NPs concentrations (10–100 µg/mL) [123]. A dose-dependent micronuclei production and DNA strand breakage have been reported in human lymphocytes by comet and micronucleus assay [124].Genotoxicity of TiO2 particles has been reported in mice after 5 days of oral exposure in addition to DNA deletions upon exposure during fetal development [125].

5.Iron oxide (Fe2O3) NPs: magnetite Fe2O3 NPs is an important candidate for drug delivery and a potential carrier for brain-targeted drug delivery [88]Induce dose-dependent DNA damage when rat alveolar macrophages and human monocyte cells at concentrations of 5.1 and 10.2 µg/cm2 [126].Micronucleus induction has been demonstrated after administration [127, 128].

6.Silica NPsAmorphous fumed silica-induced significant oxidative DNA damage in human colon epithelial cells line after 24 h of exposure [129]. Similarly, exposing human lymphoblastoid cells to 100 nm ultrafine crystalline SiO2 NPs during 6, 24, and 48 h at a range of concentrations (0-a20 mg/ml) induced genotoxicity [130].Genotoxicity has been reported in rats after a short period (1 and 3 days) inhalation of a freshly generated aerosolized amorphous SiO2 of size 37 and 82 nm, the toxicity was estimated after 24 h to 2 months after exposure [131].

7.Organic NPs: organic nanoparticles could be colloidal, e.g., polymeric NPs, solid lipid NPs, or vesicular, e.g., liposomesDendrimers are hyper-branched polymers which have been used as a promising drug delivery vehicle.
Cationic dendrimers showed increased oxidative stress and DNA damage in human neural progenitor cells dependent on surface group density and number of particles [132].