The nanostructure plays a signicant role in precipitating toxicity. Carbon nanotubes are toxic for mitochondria, for example, whereas silver nanoparticles interfere with cell membrane properties and morphology (Martinez etal., 2021). Metal nanoparticles are responsible for intracellular lipid peroxidation, leading to the damage of the plasma membrane, mitochondria, and endoplasmic retic­ulum. Metal oxide nanoparticles, such as titanium dioxide, iron oxide, and cupric oxide NP, cause an imbalance in intracellular ROS- oxidized glutathione machinery in the liver. Similarly, zinc oxide NP, administered at a dose of 50mg/kg body weight to rats, proved to be toxic for the intestine and generation of superoxide dismutase (Yang & Merlin, 2023; Catalano, 2021; Akcan et al., 2020). Another problem observed with metal/metallic oxide NP is their exceptionally low rate of clearance and, hence, the high degree of accumulation in the body. In addition to this, stable metallic NPs are more biocompatible than dissolvable metallic/metal oxide NPs. The type of NP component also affected genotoxicity. Gold and superparamagnetic iron oxide NP did not affect gene regulation or protein expression in human vein endothelial cells or adipose tissue- derived stem cells, respectively, and neither did it increase ROS production in RAW264.7 macrophages (Fröhlich, 2017). Liposomes are reported to be immunotoxic, triggering complement activation- related pseudo- allergy (CARPA) (Ray etal., 2021). Tailor- made NPs with biodegradable polymers pose a different challenge. Owing to biodegradation in vivo after predetermined and predened time duration, there are changes in their surface properties and concentration, and that may lead to immunotoxicity. Moreover, the pres­ence of anti- PEG antibodies affects the performance and may lead to the elicitation of toxic effects from PEGylated NPs. NPs of different compositions have been reported to be immunosuppressive and to act as immunomodulators, and capable of generating hypersensitivity reactions. Hydrophilic NPs as mesoporous silica NPs failed to gain access across the blood–brain barrier and are less toxic, owing to the presence of silanol groups on the surface (Yang & Merlin, 2023; Liu et al., 2022). Cerebral toxicity has been observed with charged gold and manganese dioxide nanoparticles, pre­sumably due to an increase in endocytosis capacity (Tirumala etal., 2021). To secure successful intracellular drug delivery, positively charged NPs are preferred as they can escape the endosome– lysosome degradation pathway, induce less endoplasmic reticulum stress and are less deleterious for cellular membranes and organelles, (Yang & Merlin, 2023). For NPs exhibiting differences in crys­tallinity as with titanium dioxide NP, the two forms were found to have different toxicity concerns, when studied in Balb/3T3 mouse broblasts or in human bronchial epithelium cell line. The rutile lattice showed cytotoxicity as well as genotoxicity and the cellular uptake was higher with anatase form (Abbasi etal., 2023). Amorphous forms of nano- silica were more toxic to human cell lines as they generated ROS and caused DNA cleavage (Akcan etal., 2020). Nanoparticles may be coated to achieve certain specic functions, and the coating imparts charges on the NP surface which may alter biocompatibility, biodegradation, biological functions, and, ultimately, nanotoxicity pheno­types. Coated silver NPs were found to have higher biocompatibility even at higher concentrations and to produce fewer alterations in intracellular glutathione and superoxide dismutase levels in comparison to uncoated ones, although the effects were size- dependent. The coating material also affected toxicity as citrate- coated silver NP demonstrated lower toxicity than PVP- coated ones.