Slow Release of Ions from Internalized Silver Nanoparticles Modifies the Epidermal Growth Factor Signaling Response

Due to their distinctive physiochemical properties, including a robust antibacterial activity and plasmonic capability, hundreds of consumer and medical products contain colloidal silver nanoparticles (AgNPs). However, even at sub-toxic dosages, AgNPs are able to disrupt cell functionality, through a yet unknown mechanism. Moreover, internalized AgNPs have the potential to prolong this disruption, even after the removal of excess particles. In the present study, we evaluated the impact, mechanism of action, and continual effects of 50 nm AgNP exposure on epidermal growth factor (EGF) signal transduction within a human keratinocyte (HaCaT) cell line. After AgNP expose, EGF signaling was initially obstructed due to the dissolution of particles into silver ions. However, at longer durations, the internalized AgNPs increased EGF signaling activity. This latter behavior correlated to sustained HaCaT stress, believed to be maintained through the continual dissolution of internalized AgNPs. This study raises concerns that even after exposure ceases, the retained nanomaterials are capable of acting as a slow-release mechanism for metallic ions; continually stressing and modifying normal cellular functionality

Anxiety and Depression Levels with Risk Factors of Breast Cancer Patients in Erbil City – Iraq

Background and objectives: Breast cancer appears to be becoming more common worldwide. It is the most common type of cancer in women in the Middle East and the Western countries. Patients with breast cancer are at a high risk of developing psychological problems such as anxiety and depression.  This study aimed to evaluate the severity of anxiety and depression levels in breast cancer patients and their risk factors for breast cancer. Methods: A quantitative descriptive study design was conducted at Rizgary Teaching Hospital and Nanakali Oncology Hospital in Erbil City in the Kurdistan Region of  Iraq from 1st September 2020 to 5th August 2021. The duration of data collection was four months and purposive sampling was used to select 298 patients who were admitted to both hospitals. A questionnaire format was used to gather the data, and the Hospital Anxiety and Depression Scale (HADS) standardized questionnaire was utilized to measure the level of anxiety and depression. Results: The average age of the patients was 45.28±9.17 years, 80.5% were married, 60.7% of the studied sample had a low socioeconomic status. Almost a third (30.5%) of the participants had severe anxiety and 60.4% had severe depression. Concerning the risk factors of breast cancer, 82.2% of patients were obese, 91.9% did not do exercise, 35.6% had breast cancer family history, 93.6% were non-smoker, and 6.4% of them were smokers. Conclusion: According to the findings, the majority of breast cancer patients suffer from anxiety and depression, and obesity is one of the risk factors for breast cancer

Less Is More: Long-Term in Vitro Exposure to Low Levels of Silver Nanoparticles Provides New Insights for Nanomaterial Evaluation

In view of the vast number of new nanomaterials (NMs) that require testing and the constraints associated with animal models, the majority of studies to elucidate nanotoxicological effects have occurred in vitro, with limited correlation and applicability to in vivo systems and realistic, occupational exposure scenarios. In this study, we developed and implemented a chronic in vitromodel coupled with lower, regulatory dosages in order to provide a more realistic assessment of NM-dependent consequences and illuminate the implications of long-term NM exposure. When keratinocytes were exposed to 50 nm silver nanoparticles (Ag-NPs), we determined that chronically dosed cells operated under augmented stress and modified functionality in comparison to their acute counterparts. Specifically, Ag-NP exposure through a chronic mechanism increased p38 activation, actin disorganization, heightened ki67 expression, and extensive gene modification. Additionally, chronic Ag-NP exposure altered the way in which cells perceived and responded to epidermal growth factor stimulation, indicating a transformation of cell functionality. Most importantly, this study demonstrated that chronic exposure in the pg/mL range to Ag-NPs did not induce a cytotoxic response, but instead activated sustained stress and signaling responses, suggesting that cells are able to cope with prolonged, low levels of Ag-NP exposure. In summary, we demonstrated that through implementation of a chronic dosimetry paradigm, which more closely resembles realistic NM exposure scenarios, it is possible to illuminate long-term cellular consequences, which greatly differ from previously obtained acute assessments

Physiological Fluid Specific Agglomeration Patterns Diminish Gold Nanorod Photothermal Characteristics

Investigations into the use of gold nanorods (Au-NRs) for biological applications are growing exponentially due to their distinctive physicochemical properties, which make them advantageous over other nanomaterials. Au-NRs are particularly renowned for their plasmonic characteristics, which generate a robust photothermal response when stimulated with light at a wavelength matching their surface plasmon resonance. Numerous reports have explored this nanophotonic phenomenon for temperature driven therapies; however, to date there is a significant knowledge gap pertaining to the kinetic heating profile of Au-NRs within a controlled physiological setting. In the present study, the impact of environmental composition on Au-NR behavior and degree of laser actuated thermal production was assessed. Through acellular evaluation, we identified a loss of photothermal efficiency in biologically relevant fluids and linked this response to excessive particle aggregation and an altered Au-NR spectral profile. Furthermore, to evaluate the potential impact of solution composition on the efficacy of nano-based biological applications, the degree of targeted cellular destruction was ascertained in vitro and was found to be susceptible to fluid-dependent modifications. In summary, this study identified a diminution of Au-NR nanophotonic response in artificial physiological fluids that translated to a loss of application efficiency, pinpointing a critical concern that must be considered to advance in vivo, nano-based bio-applications

Interaction of silver nanoparticles with Tacaribe virus

<p>Abstract</p> <p>Background</p> <p>Silver nanoparticles possess many unique properties that make them attractive for use in biological applications. Recently they received attention when it was shown that 10 nm silver nanoparticles were bactericidal, which is promising in light of the growing number of antibiotic resistant bacteria. An area that has been largely unexplored is the interaction of nanomaterials with viruses and the possible use of silver nanoparticles as an antiviral agent.</p> <p>Results</p> <p>This research focuses on evaluating the interaction of silver nanoparticles with a New World arenavirus, Tacaribe virus, to determine if they influence viral replication. Surprisingly exposing the virus to silver nanoparticles prior to infection actually facilitated virus uptake into the host cells, but the silver-treated virus had a significant reduction in viral RNA production and progeny virus release, which indicates that silver nanoparticles are capable of inhibiting arenavirus infection <it>in vitro</it>. The inhibition of viral replication must occur during early replication since although pre-infection treatment with silver nanoparticles is very effective, the post-infection addition of silver nanoparticles is only effective if administered within the first 2-4 hours of virus replication.</p> <p>Conclusions</p> <p>Silver nanoparticles are capable of inhibiting a prototype arenavirus at non-toxic concentrations and effectively inhibit arenavirus replication when administered prior to viral infection or early after initial virus exposure. This suggests that the mode of action of viral neutralization by silver nanoparticles occurs during the early phases of viral replication.</p

Tannic Acid Coated Gold Nanorods Demonstrate a Distinctive Form of Endosomal Uptake and Unique Distribution within Cells

One of the primary challenges associated with nanoparticle-dependent biological applications is that endosomal entrapment in a physiological environment severely limits the desired targeting and functionality of the nanoconstructs. This study sought to overcome that challenge through a systematic approach of gold nanorod (GNR) functionalization: evaluating the influence of both aspect ratio and surface chemistry on targeted cellular internalization rates and preservation of particle integrity. Owing to their unique spectral properties and enhanced surface area, GNRs possess great potential for the advancement of nanobased delivery and imaging applications. However, their ability for efficient intracellular delivery while maintaining their specific physiochemical parameters has yet to be satisfactorily explored. This study identified that longer and positively charged GNRs demonstrated a higher degree of internalization compared to their shorter and negative counterparts. Notably, of the four surface chemistries explored, only tannic acid resulted in retention of GNR integrity following endocytosis into keratinocyte cells, due to the presence of a strong protein corona matrix that served to protect the particles. Taken together, these results identify tannic acid functionalized GNRs as a potential candidate for future development in nanobased biomolecule delivery, bioimaging, and therapeutic applications

Tannic Acid Coated Gold Nanorods Demonstrate a Distinctive Form of Endosomal Uptake and Unique Distribution within Cells

One of the primary challenges associated with nanoparticle-dependent biological applications is that endosomal entrapment in a physiological environment severely limits the desired targeting and functionality of the nanoconstructs. This study sought to overcome that challenge through a systematic approach of gold nanorod (GNR) functionalization: evaluating the influence of both aspect ratio and surface chemistry on targeted cellular internalization rates and preservation of particle integrity. Owing to their unique spectral properties and enhanced surface area, GNRs possess great potential for the advancement of nanobased delivery and imaging applications. However, their ability for efficient intracellular delivery while maintaining their specific physiochemical parameters has yet to be satisfactorily explored. This study identified that longer and positively charged GNRs demonstrated a higher degree of internalization compared to their shorter and negative counterparts. Notably, of the four surface chemistries explored, only tannic acid resulted in retention of GNR integrity following endocytosis into keratinocyte cells, due to the presence of a strong protein corona matrix that served to protect the particles. Taken together, these results identify tannic acid functionalized GNRs as a potential candidate for future development in nanobased biomolecule delivery, bioimaging, and therapeutic applications

Silver and Gold Nanoparticles Alter Cathepsin Activity In vitro

Nanomaterials are being incorporated into many biological applications for use as therapeutics, sensors, or labels. Silver nanomaterials are being utilized for biological implants and wound dressings as an antiviral material, whereas gold nanomaterials are being used as biological labels or sensors due to their surface properties and biocompatibility. Cytotoxicity data of these materials are becoming more prevalent; however, little research has been performed to understand how the introduction of these materials into cells affects cellular processes. Here, we demonstrate the impact that silver and gold nanoparticles have on cathepsin activity in vitro. Cathepsins are important cellular proteases that are imperative for proper immune system function. We have selected to examine gold and silver nanoparticles due to the increased use of these materials in biological applications. This manuscript depicts how both of these types of nanomaterials affect cathepsin activity, which could impact the host's immune system and its ability to respond to pathogens. Cathepsin B activity decreases in a dose-dependent manner with all nanoparticles tested. Alternatively, the impact of nanoparticles on cathepsin L activity depends greatly on the type and size of the material

A Preliminary Assessment of Silver Nanoparticle Inhibition of Monkeypox Virus Plaque Formation

The use of nanotechnology and nanomaterials in medical research is growing. Silver-containing nanoparticles have previously demonstrated antimicrobial efficacy against bacteria and viral particles. This preliminary study utilized an in vitro approach to evaluate the ability of silver-based nanoparticles to inhibit infectivity of the biological select agent, monkeypox virus (MPV). Nanoparticles (10–80 nm, with or without polysaccharide coating), or silver nitrate (AgNO3) at concentrations of 100, 50, 25, and 12.5 μg/mL were evaluated for efficacy using a plaque reduction assay. Both Ag-PS-25 (polysaccharide-coated, 25 nm) and Ag-NP-55 (non-coated, 55 nm) exhibited a significant (P ≤ 0.05) dose-dependent effect of test compound concentration on the mean number of plaque-forming units (PFU). All concentrations of silver nitrate (except 100 μg/mL) and Ag-PS-10 promoted significant (P ≤ 0.05) decreases in the number of observed PFU compared to untreated controls. Some nanoparticle treatments led to increased MPV PFU ranging from 1.04- to 1.8-fold above controls. No cytotoxicity (Vero cell monolayer sloughing) was caused by any test compound, except 100 μg/mL AgNO3. These results demonstrate that silver-based nanoparticles of approximately 10 nm inhibit MPV infection in vitro, supporting their potential use as an anti-viral therapeutic