Nano Nightmares: Exploring the Dark Side of Nanotechnology

INTRODUCTION

Plastics have a huge impact on every aspect of daily life, including technology, medicine and pharmaceutical and household products.

Most of the plastic waste is thrown away by consumers after a single use and this waste ends up in landsfill, oceans etc. It becomes a major environmental problem when it enters the waters. Large amounts of these plastics are thrown away everyday and breakdown of plastics from nanometers has raised concerns about whether these plastics are toxic to the environment and human. While many early studies on the environment affects of nanoparticles have been reported, and little has been done to investigate their effects on the human body at the subcellular or molefcular level. In particular, how nanoparticles pass from epithelial cells of the stomach, lungs and skin to the body has not been investigated.

This review provides an in-depth look at how nanoparticles cause toxic effects on the mammalian cells and tissues.

Plastics are made from natural materials and undergo chemical processes like polymerization and polycondensation, transforming core elements into polymer chains. These materials are often reversible, and they require additional processes for recycling. Industrial additives and additives allow them to be engineered for various applications. When disposed of, plastic waste is exposed to biological, chemical, and environmental elements, breaking down into nanoparticles. Nanoparticles are less studied but the potential health impacts of nanoparticles exposure are under-studied, and this review aims to explore their creation, environmental behavior, toxicity, and potential health impacts.

origins and fate of microplastics and nanoparticles in the environment.

Less than 20% of nanoparticles come from the sea, whereas more than 80% are made on land. nanoparticles are extremely thin, unbreakable, and floatable, which allows them to travel great distances around the world. Over 800 million tonnes of plastics are thought to have come from land, according to estimates. The majority of plastics that pollute the marine environment come from terrestrial sources, fishing and other aquaculture activities, and coastal tourism. Because nanoparticles are so tiny, wastewater treatment procedures cannot remove them, and as a result, these plastic particles will enter rivers, oceans, and the fresh water supply system. Additionally, soil contains nanoparticles, which will erode naturally and release them into the environment.

Cytotoxicity and Cell Interactions:???

Researchers investigate how nanoparticles interact with cells and assess their cytotoxicity, evaluating the impact on cellular functions and viability. For instance, a study by Lin et al. (2019) examined the cytotoxic effects of silver nanoparticles on human lung epithelial cells showing with the help of figure.

Cell uptake mechanisms and intracellular fate of nanoparticles are also explored. A study by Wang et al. (2019) investigated the cellular uptake pathways of graphene oxide nanoparticles and their potential toxicity

Cell Membrane Interactions: Nanoparticles can interact with cell membranes through physical adsorption, penetration, or disruption. These interactions can affect membrane integrity, ion channels, and receptor functions, leading to cellular damage.

Cellular Uptake: Nanoparticles can be internalized by cells through various mechanisms, such as endocytosis, macropinocytosis, or direct penetration. The cellular uptake process depends on the nanoparticle properties (e.g., size, surface charge, and coating) and cell type.

Intracellular Localization: Once inside cells, nanoparticles can localize in different cellular compartments, including the cytoplasm, endosomes, lysosomes, or nucleus. Their intracellular distribution can impact cellular responses and potential toxicity.

Reactive Oxygen Species (ROS) Generation: Some nanoparticles have the ability to generate ROS, such as superoxide anions and hydroxyl radicals, either through direct interaction or by catalyzing chemical reactions. Excessive ROS production can lead to oxidative stress and damage cellular components.

Mitochondrial Dysfunction: Mitochondria are important organelles responsible for cellular energy production. Nanoparticles can cause mitochondrial dysfunction by disrupting the electron transport chain, impairing ATP synthesis, and inducing oxidative stress, leading to cellular damage.

Inflammation: Nanoparticles can trigger inflammatory responses in cells and tissues. They can activate immune cells, such as macrophages, and stimulate the release of pro-inflammatory cytokines, chemokines, and reactive molecules.

DNA Damage: Certain nanoparticles can directly interact with DNA, leading to DNA damage, including single-strand breaks, double-strand breaks, or DNA adduct formation. This can disrupt DNA replication and transcription processes, potentially causing genetic mutations.

Apoptosis and Necrosis: Exposure to certain nanoparticles can induce programmed cell death (apoptosis) or uncontrolled cell death (necrosis). These mechanisms of cell death are influenced by nanoparticle properties, cellular responses, and signaling pathways.

Cell-Specific Responses: Different cell types may exhibit varying sensitivities and responses to nanoparticles. For instance, immune cells and epithelial cells may have distinct reactions to nanoparticle exposure, highlighting the importance of considering cell-specific effects in nanotoxicology studies.

Organ specific effects

Organ specific effects refer to the specific responses and potential toxicity of nanoparticles in different organs and tissues.

Gastrointestinal Tract:

Nanoparticles that are ingested orally can interact with the cells and tissues of the gastrointestinal tract. Gastrointestinal-specific effects may involve alterations in gut microbiota, inflammation, oxidative stress, and potential disruption of intestinal barrier function. Understanding the effects of nanoparticles in the gastrointestinal tract is important for assessing oral exposure and potential toxicity. The potential of nanoparticles to permeate the gut epithelium, leading to systemic exposure in humans, is a significant issue. Historically, studies have used polystyrene nanoparticles for in vivo and in vitro tests on a variety of animals. The probable oral bioavailability level of 50 nm polystyrene nanoparticles is ten to one hundred times greater than the level of microplastics (2–7%)

Lung: The lungs are one of the primary organs exposed to nanoparticles, especially through inhalation. Certain nanoparticles, such as carbon nanotubes and silica nanoparticles, can reach the deep lung tissues and cause inflammation, oxidative stress, and even lung fibrosis. Understanding the lung-specific effects of nanoparticles is crucial due to occupational and environmental exposures.

Skin:

Nanoparticles can come into contact with the skin through topical application or from the environment. Some nanoparticles, such as titanium dioxide and zinc oxide nanoparticles used in sunscreens, have been extensively studied for their skin effects. Skin-specific effects may include oxidative stress, inflammation, and potential disruption of skin barrier function. ?scientific evidence suggested that only those nanoparticles with size below the 6–7?nm limit were able to permeate the healthy skin through the lipidic trans-epidermal, whereas nanomaterials larger than 36?nm could be preferentially absorbed by the aqueous pores or trans-follicular routes.

Liver: The liver plays a vital role in the metabolism and detoxification of foreign substances, including nanoparticles. Liver-specific effects of nanoparticles can include altered liver enzyme activity, oxidative stress, inflammation, and potential hepatotoxicity. Certain nanoparticles, such as gold nanoparticles and quantum dots, have shown interactions with liver cells and accumulation in the liver. The effects of different dose regimen on hepatotoxicity of AgNPs in rat have been studied by a few researchers [54]. They performed liver function tests and recorded the bioaccumulation of AgNPs in liver. Though elevated values for ALP were observed, other parameters showed no significant changes in comparison to controls. edema and necrosis in the liver of male ICR mice after a single intravenous (8 μmol/kg) injection of AgSe (5.1 nm) QDs were observed. However, mechanisms of cytotoxicity expressed by AgNPs have not yet been established. Silver ions released from medicaments may enter circulation facilitating translocation and accumulation in soft organs like liver.

Kidneys: The kidneys are involved in the excretion of waste products from the body, including nanoparticles. Some nanoparticles, such as metal-based nanoparticles (e.g., silver, gold, platinum, zinc, cadmium), have been found to accumulate in the kidneys and may induce nephrotoxicity. Kidney-specific effects can include oxidative stress, inflammation, and impairment of renal function.

Example-

Silver nanoparticles

• In vitro?studies:?In recent years, experimental evidence has gathered on their uptake and bioaccumulation in soft tissues.?In vitro?study showed that internalization of AgNPs in procine kidney (PK15 cells) was facilitated by endocytosis.
• In vivo?studies:?renal toxicity of AgNPs in mice and rat, adverse effects in the kidney of an African cat fish,?Clarius gariepinus?have also been reported as shown in figure.

Gold nanoparticles are now being increasingly used in drug delivery, cellular labelling, imaging and diagnosis of diseases like cancer, diabetes and Alzheimer. However, its adverse health effects are poorly known. Important applications of platinum nanoparticles include catalysis, cosmetics and dietary supplements.

• In vitro?studies:?These NPs were able to penetrate cells when incubated with renal cell sediment. The uptake of GNPs by renal proximal tubular cell line-TH1 was studied by Samkova, et al. through TEM. Bioaccumulation was determined by ICP.?
• In vivo?studies:?A detailed study on GNP toxicity in Kyoto Wistar rats was made by Abdelhalim and co-authors. These workers noted several lesions in rat kidney viz. vacuolar degeneration, cloudy swelling, hyaline droplets, and casts in the proximal tubular cells. Proximal tubules were more affected than distal tubules. Glomerular changes included hyper cellularity, mesengial cell proliferation and basement membrane thickening. These effects were attributed to ROS and diminished antioxidant mechanisms as shown in figure below.

Central Nervous System (CNS): Nanoparticles have the potential to cross the blood-brain barrier and enter the central nervous system. Studies have shown that certain nanoparticles, including metal nanoparticles and carbon-based nanomaterials, can induce neurotoxicity, oxidative stress, inflammation, and disrupt neuronal functions. Unlike the rest of the tissues, the magnitude of nanotoxic effects in CNS is often unpredictable and hazardous. Understanding the CNS-specific effects is important due to concerns regarding neurological disorders and cognitive impairments.

NPs which are well known for their potent neurotoxic effects include single-walled and multiwalled carbon nanotubes, metal oxides like SiOx , TiO2 etc., which cause worse effects in both CNS and PNS similar to that of neurotoxins.

Reproductive System:

Nanoparticles can have implications for the reproductive system, including male and female fertility and development. Studies have shown that certain nanoparticles, such as silver nanoparticles and carbon nanotubes, can affect sperm quality, hormone levels, and reproductive organ function. Understanding the reproductive system-specific effects is crucial for evaluating potential reproductive toxicity. the effect of maternal exposure to nanoparticles on the reproductive health of male offspring. the possibility of nanoparticle-induced developmental male infertility (?toxicity in testes by prenatal nanoparticle exposure.)

1) Male reproductive system

2) Female reproductive system

Example- Endometrial receptivity in female mice.

Nanoparticles (NPs) have many toxic effects on fertility and can prevent successful implantation by affecting the maternal uterine tissue. Herein, by deploying 30 female NMRI mice, the effect of silver NPs on the endometrium and implantation has been investigated. Using spherical silver NPs of a diameter of 18–30 nm at doses of 2 and 4 mg/kg, mice in two groups were treated. Then, female mice mated with male mice. Endometrial tissue was extracted 4.5 days later. On the fourth day of pregnancy, the mice were anesthetized and blood samples were taken from the heart; furthermore, endometrial tissue was isolated and used for molecular tests, inductively coupled plasma, and examination of pinopods. The results revealed that the levels of interleukin 6 (IL-6) and IL-1β and the accumulation of NPs in endometrial tissue in the group receiving NPs at a dose of 4 mg/kg had a major increase relative to the other two groups (p?< 0.05); the group receiving a dose of 4 mg/kg exhibited a decrease in pinopods and microvillus compared with the other two groups. According to the results, NPs can reach the endometrium, suggesting that caution should be exercised due to serious exposure to NPs throughout pregnancy.

Fetotoxicity of Nanoparticles (Maternal)

Due to the small size, nanoparticles have the tendency to cross the blood–placental barrier and reach the fetus, leading to various fetal abnormalities. numerous studies have indisputably demonstrated that maternal exposure to nanomaterials during gestation result in fetotoxicity, including adverse prenatal effects on the fetus, neurotoxicity, reproductive toxicity, immunotoxicity and respiratory toxicity in offspring or even in adulthood.

Maternal exposure to other metal oxide NPs during pregnancy such as CeO2?NPs and CdO NPs also led to poor pregnancy outcomes. The intravenous injection of CeO2?NPs into pregnant mice at a dose of 5 mg/kg daily from GD5–GD7 resulted in aberrations in decidualization(?the functional and morphological changes that occur within the endometrium to form the decidual lining into which the blastocyst implants.), which exhibited “ripple effects” leading to fetal loss, fetal growth retardation, placental dysfunction, and even infertility.

Bone and Skeletal System:

Nanoparticles can interact with bone cells and tissues, affecting bone health and remodeling processes. Some nanoparticles, such as hydroxyapatite nanoparticles and metallic nanoparticles, have been studied for their effects on bone cells and bone mineralization. Bone-specific effects may include alterations in bone cell activity, mineralization, and potential disruption of bone homeostasis.

Other Organs and Tissues: Nanoparticles may also have specific effects on other organs and tissues, depending on their properties, routes of exposure, and interactions within the body. For example, nanoparticles can accumulate in the spleen, lymph nodes, and adipose tissue, potentially leading to specific effects in these organs.

In conclusion, this comprehensive discussion has shed light on the negative impact of nanoparticles on mammalian cells. Nanoparticles, due to their unique physical and chemical properties, have gained considerable attention in various industries and applications. However, it is evident from the research presented that their interaction with mammalian cells can lead to detrimental effects.

Firstly, the size and surface characteristics of nanoparticles play a crucial role in determining their toxicity. Smaller nanoparticles have a greater propensity to penetrate cellular barriers, including cell membranes, leading to cellular uptake and potential damage. Additionally, surface modifications of nanoparticles can influence their cellular interactions, making it essential to consider the specific characteristics of nanoparticles when assessing their impact on mammalian cells.

Furthermore, nanoparticles have been shown to induce oxidative stress within cells. The excessive generation of reactive oxygen species (ROS) can disrupt cellular homeostasis, leading to oxidative damage to cellular components such as DNA, proteins, and lipids. This oxidative stress can trigger inflammatory responses and contribute to the development of various diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases.

The potential genotoxic effects of nanoparticles are also of significant concern. Several studies have demonstrated that nanoparticles can cause DNA damage, chromosomal aberrations, and mutations in mammalian cells. These genetic alterations can have long-lasting consequences, potentially leading to the initiation and progression of cancer.

Furthermore, the discussion highlighted the impact of nanoparticle-induced inflammation on mammalian cells. Nanoparticles can activate immune responses and trigger the release of pro-inflammatory cytokines, causing chronic inflammation. Prolonged inflammation can disrupt normal cellular functions and contribute to the pathogenesis of numerous diseases.

Importantly, the studies presented also emphasized the need for standardized and reliable toxicity assessment methods for nanoparticles. The current understanding of nanoparticle toxicity is limited, and there is a lack of consensus regarding the appropriate testing protocols and evaluation criteria. To ensure accurate and reliable assessment of nanoparticle toxicity, standardized guidelines should be established, encompassing various aspects such as physicochemical characterization, in vitro and in vivo models, and long-term effects.

In conclusion, this comprehensive discussion has demonstrated that nanoparticles can have a negative impact on mammalian cells. Their small size, surface characteristics, potential for oxidative stress, genotoxicity, and ability to induce inflammation pose significant challenges and potential risks in various fields, including medicine, consumer products, and environmental applications. It is crucial for researchers, regulators, and industry professionals to work collaboratively to develop safer nanoparticles, establish robust toxicity assessment protocols, and implement stringent regulations to mitigate the negative effects of nanoparticles on mammalian cells and overall human health.

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