This systematic review examines the cytotoxicity of silver nanoparticles (Ag-NPs) and their underlying mechanisms. Ag-NPs, widely used in various sectors due to their antimicrobial properties, can pose environmental and health risks. The review highlights the impact of Ag-NP physicochemical properties, such as size, shape, concentration, agglomeration, and surface characteristics, on their toxicity. Key findings include: 1. **Synthesis and Properties**: Ag-NPs are synthesized through various methods, including chemical reduction, gamma ray radiation, and photochemical reduction. Green synthesis methods using biological agents like bacteria and plants are gaining attention for their environmental friendliness and lower toxicity. 2. **Cytotoxicity Effects**: - **Particle Size**: Smaller Ag-NPs tend to be more toxic due to their higher surface area and reactivity. - **Concentration**: Toxicity increases with higher concentrations, but the threshold concentration varies across different cell lines. - **Coatings**: Surface coatings can stabilize Ag-NPs and reduce toxicity, with organic and inorganic coatings having different effects. - **Agglomeration**: Agglomeration affects cellular localization and toxicity, with loosely aggregated particles showing less impact. - **Surface Properties**: Surface charge, hydrophobicity, and protein corona formation influence Ag-NPs' interactions with biological systems and their toxicity. 3. **Biocidal Applications**: Ag-NPs are effective biocides against bacteria, fungi, and viruses due to their ability to release silver ions (Ag+). They are used in air filters, water treatment, and medical applications. 4. **Toxicity Mechanisms**: - **Mitochondrial Function**: Ag-NPs impair mitochondrial function, leading to oxidative stress and apoptosis. - **ROS Generation**: Excessive reactive oxygen species (ROS) cause DNA damage and protein dysfunction. - **Cellular Uptake**: Ag-NPs can enter cells through phagocytosis, endocytosis, and direct penetration. 5. **Environmental and Health Concerns**: The widespread use of Ag-NPs raises concerns about their environmental impact and potential health risks, particularly in terms of their ability to cross biological barriers and accumulate in critical tissues. The review emphasizes the need for further research to understand the complex interactions of Ag-NPs with biological systems and to develop safer synthesis and application methods.This systematic review examines the cytotoxicity of silver nanoparticles (Ag-NPs) and their underlying mechanisms. Ag-NPs, widely used in various sectors due to their antimicrobial properties, can pose environmental and health risks. The review highlights the impact of Ag-NP physicochemical properties, such as size, shape, concentration, agglomeration, and surface characteristics, on their toxicity. Key findings include: 1. **Synthesis and Properties**: Ag-NPs are synthesized through various methods, including chemical reduction, gamma ray radiation, and photochemical reduction. Green synthesis methods using biological agents like bacteria and plants are gaining attention for their environmental friendliness and lower toxicity. 2. **Cytotoxicity Effects**: - **Particle Size**: Smaller Ag-NPs tend to be more toxic due to their higher surface area and reactivity. - **Concentration**: Toxicity increases with higher concentrations, but the threshold concentration varies across different cell lines. - **Coatings**: Surface coatings can stabilize Ag-NPs and reduce toxicity, with organic and inorganic coatings having different effects. - **Agglomeration**: Agglomeration affects cellular localization and toxicity, with loosely aggregated particles showing less impact. - **Surface Properties**: Surface charge, hydrophobicity, and protein corona formation influence Ag-NPs' interactions with biological systems and their toxicity. 3. **Biocidal Applications**: Ag-NPs are effective biocides against bacteria, fungi, and viruses due to their ability to release silver ions (Ag+). They are used in air filters, water treatment, and medical applications. 4. **Toxicity Mechanisms**: - **Mitochondrial Function**: Ag-NPs impair mitochondrial function, leading to oxidative stress and apoptosis. - **ROS Generation**: Excessive reactive oxygen species (ROS) cause DNA damage and protein dysfunction. - **Cellular Uptake**: Ag-NPs can enter cells through phagocytosis, endocytosis, and direct penetration. 5. **Environmental and Health Concerns**: The widespread use of Ag-NPs raises concerns about their environmental impact and potential health risks, particularly in terms of their ability to cross biological barriers and accumulate in critical tissues. The review emphasizes the need for further research to understand the complex interactions of Ag-NPs with biological systems and to develop safer synthesis and application methods.