Silica induced toxicity

DiMatteo M, Reasor MJ. Modulation of silica-induced pulmonary toxicity hy dexamethasone-containing liposomes. Toxicol Appl Pharmacol 142(2) 411-421, 1997. 

The mechanisms of engineered photoactive nanomaterials-induced toxicity apply only partially to amorphous silica nanoparticles, mainly because their composition and structure differ from those of quantum dots, metal nanoparticles, carbon nanotubes and quartz nanoparticles. The amorphous structure and nontoxic composition provide amorphous siUca nanoparticles with a significant advantage-that is, the nanoparticle has a relatively low toxicity compared to the above-mentioned photoactive nanomaterials. Until now, studies on the toxicity of siUca nanopartides have been reported both in vitro and in vivo, as discussed below. 

In Vitro Studies of Silica Nanomaterials-induced Toxicity... 

Although the toxidties of silica nanomaterials have been investigated widely in vitro, these studies may not reflect the true scenario, as would occur with in vivo exposure. For example, a low efficiency of endocytosis might lead to a low cyto-toxidty in vitro, while severe chronic toxicity may be induced in the evacuation process. Therefore, in vivo studies are necessary in order to evaluate silica nanomaterials-induced toxicity. 

In in vivo studies, the induced toxicity of silica nanomaterials is transient, with the level of apoptosis, neutrophil and macrophage counts andcytokine/chemokine expressions returning to normal between one week and one month of recovery. 

The duration of treatment with nanomaterials in living systems is another important factor that affects silica nanomaterial-induced toxicity. Whilst for in vitro studies a greater toxicity was observed with a prolonged treatment (several days)... 

The size of the nanomaterial greatly influences its toxicity particularly as the nanomaterial s size decreases, certain of its parameters changed [3, 11, 118, 119]. Many studies have shown that variations in the size of nanomaterials account for the different toxicity levels between nanosized and micrometer-sized materials [97, 99,100,103], It is known that a reduction in size can increase the rate of uptake and translocation of silica nanomaterials in vitro and in vivo, thereby inducing a more severe and transient toxicity [56]. 

Some accessory minerals that accompany the inhaled dose of particles may themselves be reactive (such as pyrite, an iron sulfide) and may be able to modify fluid chemistry sufficiently to enhance or diminish particle solubility, or to release redox-active species such as iron. For example, the well-documented decrease in crystalline silica toxicity when combined with other, nonsilica mineral particles (SSDC, 1988) implies that the other mineral particles are reacting chemically with the body fluids and the silica to modify the surface chemistry of the silica that induces ROS generation and cytotoxicity. 

By suitably coating surgical implant materials, the tendency of the latter to induce thrombosis is greatly reduced. Co-polymerisation of dipalmitylphosphatidyl choline and alkyl methacrylate, for example, results in coatings which are stable, non-toxic, anti-inflammatory and devoid of other unwanted bioeffects. Some phospholipids can be immobilised by attachment to the surface of silica... 

A number of studies [18] submission of information on in vitro and in vivo toxicity of silica nanoparticles - both crystalline and amorphous. Most of the results on the toxicity in vitro is reduced to the analysis of size - and dose-dependent cytotoxicity, increased reactive oxygen species and proinflammatory stimulation. The data obtained from in vivo studies demonstrate nanoparticles induced lung inflammation and fibrosis, emphysema, and granuloma formation. It is therefore important to monitor the content of nano-sized silica in the body. 

Pulmonary exposure is the most popular route for in vivo investigations of nanomaterials-induced toxidty. In order to better understand the toxic effect of amorphous silica nanomaterials, the nanomaterials were instilled into the respiratory tract [38, 44—46, 100] and, after a period of treatmenf the acute and subacute pulmonary toxic effects were monitored. However, this phenomenon was an induced transient toxicity, and pulmonary function was fully recovered after several days post-exposure. Compared to the persistent pulmonary inflammation caused by crystalline silica nanomaterials, the negative effect of amorphous silica nanomaterials was considered insignificant. 

Dopants may also leak from the silica matrix, and if this occurs then the toxicity of the silica nanomaterials will be altered. However, under certain circumstances, leakage can be deliberately induced, an example being in the case of drug delivery. Here, anticancer drugs can be doped inside a siUca matrix and then delivered to target cells [15, 21, 26] the subsequent intracellular release of the drug molecules would then result in death of the cancer cells. 

Prolonged inhalation of dusts by humans (156), rodents (157,158), and other species (159,160) is associated with an increase in the number of type II cells and increased secretion of surfactant. The stimulation of surfactant appears to be directly related to the toxicity of the dust. It may be so florid, as in acute silicosis, that flooding of the alveolar spaces with surfactant lipids and associated proteins may occur, a condition known as alveolar lipoproteinosis (156). In experimental lipoproteinosis in the rat, the major lipid component is disaturated phosphatidylcholine (157), but all lipid fractions are increased. In the sheep model of experimental silicosis, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylinositol, showed the greatest increases following silica exposure (159). The excess production of surfactant in response to silica dust may be an adaptive response, perhaps to reduce particle cytotoxicity or to compensate for oxidant-induced lipid peroxidation (147,161). 

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