Silver nanoparticles: Synthesis, medical applications and ...

Silver nanoparticles (AgNPs) have emerged as a fascinating category of nanomaterials in the realm of biomedicine, attributed to their distinctive physicochemical characteristics. This article explores the latest advancements in AgNPs, including their synthesis techniques, medical applications, and biosafety concerns. The synthesis of AgNPs can be achieved through various methods, such as physical, chemical, and biological processes. Predominantly, AgNPs are employed in antimicrobial and anticancer therapies, wound healing, bone regeneration, vaccine adjuvants, anti-diabetic agents, and biosensors. The review also discusses the biological mechanisms of AgNPs, focusing on the release of silver ions (Ag +), production of reactive oxygen species (ROS), and disruption of cell membrane structures. Despite the significant therapeutic potential, there are concerns regarding their toxicity on cells, tissues, and organs. In addition, the introduction of silver Ångstrom particles (AgÅPs), smaller than AgNPs, demonstrates superior biological activity and reduced toxicity. The article also highlights current challenges and future development directions for AgNPs.

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Considering the incorporation of AgNPs in various products such as dressings, creams, solvents, and scaffolds, it's crucial to evaluate their potential toxicity in cells, tissues, and organs. The primary exposure routes include skin contact, inhalation, ingestion, and injection. These routes enable the distribution of AgNPs across different systems, including the skin, respiratory, circulatory, nervous, hepatobiliary, urinary, and reproductive systems. Deposited AgNPs can potentially cause toxicity by inducing cell death, genetic mutations, or functional impairments in these systems. For instance, AgNPs in the lungs may lead to pneumonia and asthma, while crossing the blood-testis barrier (BTB) could reduce fertility and cause deformities in offspring. Research indicates that the toxicity of AgNPs is associated with their properties, such as surface area and the release of silver ions (Ag +), as well as factors like dosage, concentration, and exposure time. Investigating the pharmacodynamics of AgNPs in vivo could aid in developing safer biocompatible agents.

In recent years, AgNPs have shown significant anticancer properties. Both in vitro and in vivo studies have demonstrated the efficacy of AgNPs against various cancers, including cervical, breast, lung, liver, nasopharyngeal, colorectal, and prostate cancers. The anticancer activity of AgNPs depends on their inherent properties like size, shape, and surface charge, with smaller particles generally exhibiting higher biological activity. To design effective anticancer agents, smaller Ag particles have been synthesized, which exhibit enhanced anticancer activity compared to AgNPs. Key factors like exposure time and dosage also play crucial roles in anticancer efficacy. AgNPs induce apoptosis or necrosis by disrupting cancer cell structures, generating ROS, damaging DNA, inactivating enzymes, and regulating signaling pathways. Additionally, AgNPs can inhibit tumor invasion and metastasis by preventing angiogenesis. Tumor cells preferentially absorb nanoparticles due to the enhanced permeability and retention (EPR) effect, which enhances targeted drug delivery of AgNPs. Further research into the anticancer mechanisms of AgNPs is essential to develop cost-effective, reliable, and broad-spectrum anticancer agents.

Numerous studies have focused on synthesizing size- and shape-controlled AgNPs, employing methods like physical, chemical, and biological techniques. Physical methods primarily involve mechanical and vapor-based processes, such as milling, pyrolysis, and spark discharge, which yield uniform-sized and high-purity AgNPs. Chemical synthesis, the most common method, involves the reduction of silver ions to silver atoms, consisting of nucleation and growth phases. This method allows precise control over the size and shape of AgNPs by regulating the nucleation and growth rates. Along with reducing agents, capping agents and stabilizers are important for achieving well-dispersed and uniform nanoparticles. External energy sources like microwave, light, heat, and sound can also assist in the synthesis process. However, the potential toxicity and pollution from chemicals used in these methods must be considered. Compared to physical and chemical methods, biological synthesis offers an eco-friendly and cost-effective approach. Various microorganisms, including bacteria, fungi, algae, and plant extracts, have been employed in the biological synthesis of AgNPs due to their abundance of organic compounds that can reduce silver salts. These organic substances can also act as stabilizers and capping agents, impacting the subsequent medical applications of AgNPs.

Silver and its compounds have been used for their antibacterial and therapeutic properties for centuries. From ancient Greeks and Romans using silverware to store water and food, to Hippocrates treating ulcers with silver preparations, and more recently, silver nitrate for wound care and disinfection were common practices. In the 19th century, silver preparations were developed for treating wound infections and burns, but their medical use declined with antibiotics' advent. However, with the widespread issue of antibiotic resistance and the advancement of nanotechnology, silver has regained attention in recent years.

Potential Toxicity of AgNPs

The potential hazards of nanomaterials to organs and systems in the body have been increasingly recognized, impacting their biomedical applications. Therefore, it's crucial to review the in vivo dynamics of AgNPs. AgNPs can be absorbed and distributed in various organs through different routes, such as inhalation, ingestion, skin contact, and subcutaneous or intravenous injection. The absorbed AgNPs can be found in systems like the dermis, respiratory, spleen, digestive, urinary, nervous, immune, and reproductive systems, with particular deposition in the spleen, liver, kidney, and lung. Small-sized AgNPs can easily penetrate biological barriers like the blood-brain barrier and blood-testis barrier, inducing potential cytotoxicity. Non-specific distribution of AgNPs may lead to toxicities such as dermal toxicity, ocular toxicity, respiratory toxicity, hepatobiliary toxicity, neurotoxicity, and reproductive toxicity. The cytotoxic potential depends on administration routes and AgNP characteristics, such as size, shape, and concentration. At the cellular level, studies have shown that AgNPs can induce chemical transformations leading to cytotoxicity, involving forms like Ag0, Ag-O-, and Ag-S- species. However, more research is needed to fully understand the long-term adverse health effects and mechanisms of AgNP toxicity in different tissues and organs. To develop biocompatible AgNPs for medical applications, a systematic study of their potential cytotoxicity is essential.

Table 6

Even as early as 1622, Angelo Sala reported the first case of argyria, a condition caused by silver deposition in tissues. This mid-19th-century recognition indicated that silver and silver compounds might cause permanent gray-blue pigmentation of skin and mucous membranes. The skin, as the largest organ and a primary barrier, plays an essential role in isolating external pathogens from the body. Topically applied AgNPs can penetrate the skin and accumulate, potentially causing cytotoxicity. The penetration pathways primarily include follicular and intercellular routes. Yu Kyung Tak et al. observed differing behaviors of AgNPs of various shapes in the skin, with rod-shaped, spherical, and triangular AgNPs penetrating the dermis, epidermis, and stratum corneum, respectively. Their study indicated that prolonged exposure increased nanoparticle amounts. Francesca et al. demonstrated more significant penetration of AgNPs on damaged skin compared to intact skin. Radoslaw et al. explored AgNP cytotoxicity on epidermal keratinocytes (NHEK), finding inhibited cell proliferation and migration, activation of caspases, and DNA damage. These studies highlight the skin as a significant site for potential AgNP-induced cytotoxicity due to its role as a barrier.

Eye Toxicity

AgNPs can cause transient conjunctival irritation, dependent on concentration, without reliable evidence of toxicological effects. Pattwat et al. investigated whether colloidal AgNPs caused acute eye irritation or corrosion in guinea pigs, finding only transient conjunctival hyperemia with high-dose treatment but no toxicological effects. AgNPs may pose developmental toxicity risks, leading to various eye defects during early life stages, as shown by Yuan Wu et al.'s study on Japanese medaka. Their findings highlighted potential morphological abnormalities and eye defects such as microphthalmia, exophthalmia, and others, suggesting complex toxicological mechanisms at play.

Respiratory Toxicity

AgNPs can induce acute lung toxicity and impair lung function. Studies have shown that nanoparticles can cross the air-blood barrier, leading to inflammation and tissue damage, with smaller particles causing more severe effects. Kaewamatawong et al. demonstrated a dose-dependent acute lung toxicity in mice, identifying bronchitis, alveolitis, and proinflammatory cytokine involvement. Joanna et al. found that AgNPs could trigger asthma by disrupting blood/alveolar permeability barriers and eliciting eosinophilic inflammation.

Hepatobiliary System Toxicity

AgNPs tend to accumulate in the liver, causing hepatobiliary damage and inflammation. Studies have shown size- and dose-dependent liver toxicity, with Kupffer cells playing a significant role in nanoparticle removal. Maglie et al. and Camilla et al. reported severe hepatocyte necrosis and gallbladder hemorrhage, emphasizing the liver as a critical site for nanoparticle-induced cytotoxicity.

Central Nervous System Toxicity

AgNPs can penetrate the brain, leading to neuronal death and neuroinflammation. Studies have shown that AgNPs induce intracellular ROS generation, apoptosis, and inflammatory cytokine secretion in astrocytes. Liming et al.'s research highlighted potential neuroinflammation and oxidative stress mechanisms. AgNPs may weaken blood-brain barriers, impairing cognitive functions and increasing Alzheimer’s disease risks.

Kidney Toxicity

The kidneys play crucial roles in balancing body fluids and detoxifying the body. AgNPs can accumulate in the kidneys, disrupting renal function and causing gender-related silver accumulation differences. Studies indicate dose-dependent cytotoxicity, with smaller AgNPs causing more severe effects. Renal metallothioneins and organic anions may influence silver accumulation and clearance in the kidneys.

Immune System Toxicity

AgNPs can affect the immune system by influencing cytokine production and immune cell viability. Wim et al. reported that AgNPs led to increased spleen size and significantly inhibited NK cell activity. This suggests the immune system's sensitivity to nanoparticle exposure, leading to potential adverse effects on immune function.

Reproductive System Toxicity

AgNPs can cross biological barriers such as the blood-testis barrier, causing reproductive system toxicity. Studies have shown size-, time-, and dose-dependent cytotoxicity in germ cells and related structures. Zhang et al. found decreased testosterone production and impaired spermatogonial stem cell function in AgNPs-treated cells. AgNPs can also accumulate in offspring, affecting their development and fecundity, as suggested by Cynthia et al.'s study on Drosophila.

Nano Silver Powder (Ag) Description

Nano Silver Powder (Ag), also known as silver nanoparticles or colloidal silver, consists of minuscule particles typically below 100 nanometers. These particles exhibit distinctive properties due to their vast surface area-to-volume ratio, which enhances their reactivity and efficacy in various applications.

Nano Silver Powder is recognized for its antimicrobial and antibacterial capabilities. The nanoparticles release silver ions that can inhibit the proliferation of bacteria, fungi, and other microorganisms, making it valuable in medical, textile, and water treatment industries for products such as wound dressings, antibacterial coatings, and disinfectants.

Additionally, Nano Silver Powder finds uses in electronics, catalysis, and as a conductor in conductive inks and pastes, owing to its excellent electrical and thermal conductivity. It is also employed in the manufacturing of printed circuit boards, solar cells, conductive adhesives, and sensors.

Nano Silver Powder (Ag) Specification

CAS Number

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# -22-4

Purity

99.9%

Chemical Formula

Ag

Morphology

Nearly spherical

APS

50nm

Specific Surface Area (m2/g)

30

Bulk Density (g/cm3)

1.24

Tap Density (g/cm3)

3.39

Color

Gray

Silver Powders Comparison

Nano Silver Powder (Ag) Applications

1. Antibacterial and antimicrobial applications: Nano Silver Powder has potent antibacterial and antimicrobial properties, making it suitable for use in healthcare settings, such as wound dressings, ointments, and medical equipment coatings. It can also be used in water purification systems to eliminate harmful bacteria and pathogens.

2. Electronics and electrical industry: Nano Silver Powder is used in the manufacturing of conductive inks and pastes, which can be employed in printed electronics, flexible electronics, and circuit boards. It provides excellent electrical conductivity and allows for miniaturization of electronic components.

3. Textile industry: Nano Silver Powder can be incorporated into textiles to create antimicrobial and odor-resistant fabrics. It can be applied to clothing, bedding, and other textile products to prevent the growth of bacteria, fungi, and other microorganisms.

4. Cosmetics and personal care products: Nano Silver Powder is used in skincare products, such as creams, lotions, and soaps, due to its antimicrobial properties. It can be effective against acne-causing bacteria and helps in maintaining hygiene and preventing skin infections.

5. Energy applications: Nano Silver Powder is utilized in the production of electrodes for fuel cells, batteries, and supercapacitors. It enhances the conductivity and stability of these energy storage devices, improving their efficiency and performance.

6. Catalysts: Nano Silver Powder can act as an excellent catalyst in various chemical reactions due to its high surface area and unique reactivity. It is used in catalytic converters, chemical synthesis, and environmental applications, such as air and water purification.

7. Coatings and paints: Nano Silver Powder can be incorporated into coatings and paints to provide antimicrobial properties, preventing the growth of bacteria and mold on surfaces. It can be applied to walls, roofs, and other surfaces to maintain cleanliness and hygiene.

8. Food packaging: Nano Silver Powder is used in food packaging materials to extend the shelf life of food products. It acts as a barrier against bacteria and other pathogens, reducing the risk of food spoilage and contamination.

9. Photovoltaic cells: Nano Silver Powder is used in the production of solar cells and photovoltaic panels. It helps in enhancing electrical conductivity, reducing resistance losses, and improving overall efficiency.

10. Automotive industry: Nano Silver Powder is utilized in the manufacturing of coatings and paints for automobiles. It provides protection against corrosion, UV radiation, and microbial growth, improving the durability and aesthetics of automotive components.

Nano Silver Powder (Ag) Safety Information

Signal Word

Warning

Hazard Statements

H400-H410

Hazard Codes

Xn,N

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