In vivo Genotoxicity of Silver Nanoparticles after 90-day Silver Nanoparticle Inhalation Exposure

Abstract In this study we show for the first time that a reduced graphene oxide (rGO) carrier has a 15-fold higher catalysis rate than graphene oxide (GO) in Ag+ reduction. Based on this, we constructed a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which unlocked an Ag+ prodrug to generate silver nanoparticles and inhibited the growth of various tumors. In this bioreactor system, intratumoral H2O2 acted as the reductant and the rGO carrier acted as the catalyst. Chelation of aptamers to this prodrug increased the production of silver nanoparticles by tumor cells, especially in the presence of Vitamin C, which broke down in tumor cells to supply massive amounts of H2O2. Consequently, highly efficient silver nanoparticle-induced apoptosis was observed in HepG2 and A549 cells in vitro and in HepG2- and A549-derived tumors in vivo. The apoptosis was associated with ROS-induced changes in mitochondrial membrane potential and DNA damage. The specific aptamer targeting and intratumoral silver nanoparticle production guaranteed excellent biosafety, with no damage to normal cells, because the Ag+ prodrug was specifically unlocked in tumors. More significantly, there was no evident tissue damage in monkeys, which greatly increases the clinical translation potential of the SEOB system.

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Detection of intracellular silver nanoparticles using flow cytometry

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2018.04.223-226 ◽

2018 ◽

pp. 223-226

Author(s):

С.И. Каба ◽

А.А. Соколовская

Keyword(s):

Flow Cytometry ◽

Silver Nanoparticles ◽

Endothelial Cells ◽

Silver Nanoparticle ◽

Cell Uptake ◽

Control Samples

Продемонстрировано обнаружение наночастиц серебра во внутриклеточном пространстве с помощью проточной цитофлуориметрии. В эндотелиальных клетках линии EA.hy926, инкубированных в растворе, содержащем 2 мкг/мл наносеребра, измеряли боковое светорассеяние. По сравнению с контрольными образцами этот параметр возрастал, в то время как прочие значимые характеристики не изменялись. Это подтверждает чувствительность метода к изменившемуся состоянию клеток и указывает на поглощение наночастиц серебра клетками при концентрации ниже токсической. The study demonstrated a possibility for detection of intracellular silver nanoparticles using flow cytometry. The parameter used in this work, side scattering, was measured in EA.hy926 endothelial cells incubated in a 2 mg/ml silver nanoparticle solution. This parameter was increased compared to control samples. Therefore, this technique was sensitive to changes in the cell status and suggested the cell uptake of the particles under the subtoxic conditions.

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Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666201211100830 ◽

2020 ◽

Vol 23 ◽

Author(s):

Hossam Ebaid ◽

Mohamed Habila ◽

Iftekhar Hassan ◽

Jameel Al-Tamimi ◽

Mohamed S. Omar ◽

...

Keyword(s):

Dna Damage ◽

Silver Nanoparticles ◽

Nuclear Dna ◽

Liquid Paraffin ◽

Tail Length ◽

Hepatic Tissue ◽

Tissue Destruction ◽

Group 2 ◽

The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

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An insight into the determination of size and number concentration of silver nanoparticles in blood using single particle ICP-MS (spICP-MS): Feasibility of application to samples relevant to in vivo toxicology studies

Journal of Analytical Atomic Spectrometry ◽

10.1039/d1ja00068c ◽

2021 ◽

Author(s):

Isabel Abad-Álvaro ◽

Diego Leite ◽

Dorota Bartczak ◽

Susana Cuello ◽

Beatriz Gomez-Gomez ◽

...

Keyword(s):

Silver Nanoparticles ◽

Single Particle ◽

Number Concentration ◽

Biological Matrices ◽

Icp Ms ◽

Toxicological Studies ◽

Insight Into

Toxicological studies concerning nanomaterials in complex biological matrices usually require a carefully designed workflow that involves handling, transportation and preparation of a large number of samples without affecting the nanoparticle...

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Silver Nanoparticles and Their Antibacterial Applications

International Journal of Molecular Sciences ◽

10.3390/ijms22137202 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7202

Author(s):

Tamara Bruna ◽

Francisca Maldonado-Bravo ◽

Paul Jara ◽

Nelson Caro

Keyword(s):

Silver Nanoparticles ◽

Antibacterial Agents ◽

Multidrug Resistant ◽

Secondary Effects ◽

Cytotoxic Effects ◽

Factors Affecting ◽

Gram Positive Bacteria ◽

Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

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A comparative study of silver nanoparticle dissolution under physiological conditions

Nanoscale Advances ◽

10.1039/d0na00733a ◽

2020 ◽

Vol 2 (12) ◽

pp. 5760-5768

Author(s):

Lukas Steinmetz ◽

Christoph Geers ◽

Sandor Balog ◽

Mathias Bonmarin ◽

Laura Rodriguez-Lorenzo ◽

...

Keyword(s):

Silver Nanoparticles ◽

Comparative Study ◽

Silver Nanoparticle ◽

Biologically Relevant ◽

Physiological Conditions ◽

Aggregation Behaviour

The dissolution and aggregation behaviour of silver nanoparticles under physiological conditions and in biologically relevant environments is investigated by exploiting their plasmonic properties.

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Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

Toxicological Sciences ◽

10.1093/toxsci/kfab049 ◽

2021 ◽

Author(s):

Shu-Chieh Hu ◽

Matthew S Bryant ◽

Estatira Sepehr ◽

Hyun-Ki Kang ◽

Raul Trbojevich ◽

...

Keyword(s):

Human Lung ◽

Inhalation Exposure ◽

Systemic Exposure ◽

Sprague Dawley ◽

Oral Gavage ◽

Sd Rats ◽

New Information ◽

Sprague Dawley Rats ◽

Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

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The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms

BMC Nephrology ◽

10.1186/s12882-021-02428-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hamed Nosrati ◽

Manijeh Hamzepoor ◽

Maryam Sohrabi ◽

Massoud Saidijam ◽

Mohammad Javad Assari ◽

...

Keyword(s):

Silver Nanoparticles ◽

Molecular Mechanisms ◽

Renal Toxicity ◽

Periodic Acid ◽

Critical Role ◽

Oral Exposure ◽

Control Group ◽

Rt Pcr ◽

Periodic Acid Schiff

Abstract Background Silver nanoparticles (AgNPs) can accumulate in various organs after oral exposure. The main objective of the current study is to evaluate the renal toxicity induced by AgNPs after repeated oral exposure and to determine the relevant molecular mechanisms. Methods In this study, 40 male Wistar rats were treated with solutions containing 30, 125, 300, and 700 mg/kg of AgNPs. After 28 days of exposure, histopathological changes were assessed using hematoxylin-eosin (H&E), Masson’s trichrome, and periodic acid-Schiff (PAS) staining. Apoptosis was quantified by TUNEL and immunohistochemistry of caspase-3, and the level of expression of the mRNAs of growth factors was determined using RT-PCR. Results Histopathologic examination revealed degenerative changes in the glomeruli, loss of tubular architecture, loss of brush border, and interrupted tubular basal laminae. These changes were more noticeable in groups treated with 30 and 125 mg/kg. The collagen intensity increased in the group treated with 30 mg/kg in both the cortex and the medulla. Apoptosis was much more evident in middle-dose groups (i.e., 125 and 300 mg/kg). The results of RT-PCR indicated that Bcl-2 and Bax mRNAs upregulated in the treated groups (p < 0.05). Moreover, the data related to EGF, TNF-α, and TGF-β1 revealed that AgNPs induced significant changes in gene expression in the groups treated with 30 and 700 mg/kg compared to the control group. Conclusion Our observations showed that AgNPs played a critical role in in vivo renal toxicity.

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