IndexIntroductionResearchFactors influencing NP toxicityIntroductionUnfortunately, there are limited data regarding NP toxicity and immunological reactions. Although various in vitro tests are conducted to evaluate the toxicity of NPs, no single standards exist to evaluate their potential immunotoxicity. In most previous studies, NPs have been confirmed without obvious toxic or immunological responses. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Ideal NPs are avoided by the immune system and maintain their integrity in different biological environments to improve the effectiveness of targeted delivery. Few studies have examined the interactions between NPs and the immune system (complement, blood components) and its effects on the biodistribution of NPs. Therefore, the merits of the application of NPs still face the indispensable concern of toxic or immunological side effects. ResearchHubbs et al. demonstrated that the circulation of NPs is conducted through the lymphatic system. Therefore, the immune system distinguishes NPs from other traditional drugs, which could initiate immunological reactions [240]. In two other studies, particle-specific antibody production occurred by conjugation of C60 fullerene NP derivatives with a protein carrier. But, in other studies associated with fullerene derivatives, gold colloids, cationic polyamidoamine, and dendrimers, no particle-specific immune response was found. In one study, 20 and 100 nm GNPs were administered intravenously to mice. Although the 20 nm GNPs penetrated the BRB and were detected in the retinal layers, no structural abnormalities and increased cell death occurred. However, Sandrian et al. reported ocular inflammation in mice after intravitreal injection of gold nanorods, as a contrast agent for OCT. Therefore, weighing the possible toxic and immunological effects of NPs, reliable testing methods should be conducted before using NPs in therapeutic or diagnostic methods. Factors that influence the toxicity of NPs There are many factors that determine the toxicity of NPs in tissues including the eye, such as their size, charge, structure, biodistribution and evaluation time. There are some studies conducted to evaluate the toxicity of NPs based on their concentration, the length of the polymer tails and their various nature. It has been suggested that among these decisive factors, the size and intensity of NPs have the most important role regarding toxicity. In a study regarding the impacts of silica NPs on neuronal cells, the smaller one (50 nm) caused cell apoptosis versus the larger one (200 nm). It appears that the size-dependent toxicity of silica is influenced by the intracellular calcium concentration. Copper NPs reflect the same outcome regarding toxicity. Copper NPs with sizes of 40 nm had severe toxic effects in contrast to NPs of 60 and 80 nm. Some other studies have concluded that the size of NPs drastically affects their interactions with the lymphatic system. Therefore, smaller NPs (25 nm or smaller), especially with surface charge, have significant antigenic properties. These results could be implied by the fact that smaller NPs due to their larger surface area have more interfaces with surrounding materials. In some studies, considering immunological aspects, the size of some NPs (e.g. gold, polymers, lipids) influences the induction of cytokines.