Nps Toxicity and Immunologic Reactions

Introduction

Unfortunately, there are limited data regarding NPs toxicity and immunologic reactions. Although various in vitro tests are conducted for evaluating NPs toxicity, there are not unique standards for evaluating their potential immunotoxicity. In most of previous studies, NPs has been confirmed with no evident toxic or immunologic responses.

Ideal NPs are avoided from immune system and maintain their integrity in different biological environments for enhancing targeted delivery efficacy. Few studies have reviewed interactions between NPs and immune system (complement, blood components) and its effects on NPs biodistribution. So, merits of NPs application still face with indispensable concern of toxic or immunologic side-effects.

Research

Hubbs et al. have demonstrated that circulation of NPs is conducted via lymphatic system. So, immune system distinguishes NPs from other traditional drugs, which could initiate immunologic reactions [240]. In another two studies there was production of particle specific antibodies by conjugation of C60 fullerene NPs derivatives with a protein carrier. But, in other studies associated with fullerene derivatives, gold colloids, cationic poly amidoamine and dendrimers, there was no particle-specific immune response.

In one study 20 and 100 nm GNPs were intravenously administered into the mice. Although 20 nm GNPs penetrated BRB and were detected in retinal layers, there was no structural abnormality and rising of cellular death. However, Sandrian et al. reported mice ocular inflammation after intravitreal injection of golden nanorods, as a contrast agent for OCT.

So, by pondering possible toxic and immunologic effects of NPs, reliable testing methods should be conducted before usage of NPs in therapeutic or diagnostic methods.

Factors affecting NPs toxicity

There are multiple factors determining NPs toxicity in tissues including eye, such as their size, charge, structure, biodistribution and time of assessment. There are some studies conducted assessing toxicity of NPs based on their concentration, length of polymer tails and their various kinds. It has been suggested that among those decisive factors, NP’s size and intensity have the most serious role about toxicity. In one study related to impacts of silica NPs on neuronal cells, smaller one (50 nm) caused cellular apoptosis against larger one (200 nm). It seems that silica size depended toxicity is affected by intracellular calcium concentration.

The copper NPs reflected the same out comes regarding toxicity. Copper NPs with 40 nm size had serious toxic effects in contrast with 60 and 80 nm NPs. Some other studies concluded that NP’s size drastically effects on their interactions with lymphatic system. Thus, smaller NPs (25 nm or smaller) especially with surface charge have meaningful antigenic properties. These results could be implied by this fact that smaller NPs by their larger surface have more interfaces with their surrounding materials.

In some studies, by considering immunologic aspects, some NP’s (e.g. gold, polymer, lipid,) size is influential on inducing cytokines by their loaded antigens. Some other NPs toxicity like zinc oxide (ZnO2) is basically dependent on their concentration not their size.

As it stated, charge and surface chemistry of NPs are other determining factors regarding their toxicity in various tissues. Dobrovolskaia et al. demonstrated that immunological responses of NPs is greatly affected by their surface chemistry that could be modified. In one hand, positively charged NPs (like LPD) have successful uptake by negatively charged cellular membrane. On the other hand, this mechanism might facilitate cell membrane functional impairment.

Cationic NPs might adhere to negatively charged components of vitreous. This mechanism leads to accumulation of cationic NPs in vitreous, restriction in retinal target therapy and more possibility of toxicity. Based on some studies, cationic NPs could be more toxic according to their interactions with some components of cell membrane and DNA compared to anionic NPs.

In some other cases like Titanium Dioxide NPs (TiO2), longer period administration had prominent functional impairments by enhancing oxidative damage in ocular neural cells. Eom et al. assessed the effects of TiO2 on rabbits’ ocular surface. Though tear secretion did not affect by TiO2 NPs, there was considerable damage regarding ocular surface and conjunctival cells. On the contrary, exposure with lower dosage of TiO2 NPs in shorter periods of time did not cause retinal toxicity.

Likewise, long term presence of albumin NPs encapsulating ganciclovir did not induce retinal disorders or immunologic reactions. There was a substantial accumulation of materials near to retina, which was well tolerated by photoreceptors and other close areas in rabbit eye. Wong et al. have reported the safety of cerium oxide NPs after single intravitreal administration in normal rat retina.