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1.
ALTEX ; 39(2): 183­206, 2022.
Article in English | MEDLINE | ID: mdl-34874455

ABSTRACT

Engineered nanomaterials (ENMs) come in a wide array of shapes, sizes, surface coatings, and compositions, and often possess novel or enhanced properties compared to larger sized particles of the same elemental composition. To ensure the safe commercialization of products containing ENMs, it is important to thoroughly understand their potential risks. Given that ENMs can be created in an almost infinite number of variations, it is not feasible to conduct in vivo testing on each type of ENM. Instead, new approach methodologies (NAMs) such as in vitro or in chemico test methods may be needed, given their capacity for higher throughput testing, lower cost, and ability to provide information on toxicological mechanisms. However, the different behaviors of ENMs compared to dissolved chemicals may challenge safety testing of ENMs using NAMs. In this study, member agencies within the Interagency Coordinating Committee on the Validation of Alternative Methods were queried about what types of ENMs are of agency interest and whether there is agency-specific guidance for ENM toxicity testing. To support the ability of NAMs to provide robust results in ENM testing, two key issues in the usage of NAMs, namely dosimetry and interference/bias controls, are thoroughly discussed.


Subject(s)
Animal Testing Alternatives , Nanostructures , Animals , Nanostructures/chemistry , Nanostructures/toxicity , Toxicity Tests/methods
2.
Nanomicro Lett ; 10(3): 53, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30079344

ABSTRACT

Graphene-based nanomaterials (GBNs) have attracted increasing interests of the scientific community due to their unique physicochemical properties and their applications in biotechnology, biomedicine, bioengineering, disease diagnosis and therapy. Although a large amount of researches have been conducted on these novel nanomaterials, limited comprehensive reviews are published on their biomedical applications and potential environmental and human health effects. The present research aimed at addressing this knowledge gap by examining and discussing: (1) the history, synthesis, structural properties and recent developments of GBNs for biomedical applications; (2) GBNs uses as therapeutics, drug/gene delivery and antibacterial materials; (3) GBNs applications in tissue engineering and in research as biosensors and bioimaging materials; and (4) GBNs potential environmental effects and human health risks. It also discussed the perspectives and challenges associated with the biomedical applications of GBNs.

3.
Environ Sci Technol ; 50(16): 8840-8, 2016 08 16.
Article in English | MEDLINE | ID: mdl-27390928

ABSTRACT

A combination of silver nanoparticles (AgNPs) and an antibiotic can synergistically inhibit bacterial growth, especially against the drug-resistant bacteria Salmonella typhimurium. However, the mechanism for the synergistic activity is not known. This study chooses four classes of antibiotics, ß-lactam (ampicillin and penicillin), quinolone (enoxacin), aminoglycoside (kanamycin and neomycin), and polykeptide (tetracycline) to explore their synergistic mechanism when combined with AgNPs against the multidrug-resistant bacterium Salmonella typhimurium DT 104. Enoxacin, kanamycin, neomycin, and tetracycline show synergistic growth inhibition against the Salmonella bacteria when combined with AgNPs, while ampicillin and penicillin do not. UV-vis and Raman spectroscopy studies reveal that all these four synergistic antibiotics can form complexes with AgNPs, while ampicillin and penicillin do not. The presence of tetracycline enhances the binding of Ag to Salmonella by 21% and Ag(+) release by 26% in comparison to that without tetracycline, while the presence of penicillin does not enhance the binding of Ag or Ag(+) release. This means that AgNPs first form a complex with tetracycline. The tetracycline-AgNPs complex interacts more strongly with the Salmonella cells and causes more Ag(+) release, thus creating a temporal high concentration of Ag(+) near the bacteria cell wall that leads to growth inhibition of the bacteria. These findings agree with the recent findings that Ag(+) release from AgNPs is the agent causing toxicity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Silver/chemistry , Drug Synergism , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests
4.
Chem Biol Drug Des ; 87(1): 154-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26242248

ABSTRACT

Current treatment options for human African trypanosomiasis (HAT) are ineffective, and they have several well-known clinical limitations. In our continued efforts to identify chemotypes that can be developed into clinically useful drugs, we screened a targeted compound library against the major cathepsin L (rhodesain) in T. brucei. We report the antirhodesain activity and antitrypanosomal activity of the compounds in this letter. The identified compounds can serve as starting points for structure- and/or phenotype-based lead optimization strategy against Trypanosoma brucei.


Subject(s)
Cathepsin L/antagonists & inhibitors , Trypanocidal Agents/pharmacology , Trypanosoma brucei brucei/enzymology , Hep G2 Cells , Humans
5.
Bioorg Med Chem Lett ; 25(20): 4509-12, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26342866

ABSTRACT

Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active against rhodesain and T. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary SAR studies. We envision that in vitro enzymatic assays will further expand the use of the covalent tethering method, a simple fragment-based drug discovery technique to discover covalent drug leads.


Subject(s)
Cysteine Endopeptidases/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Cysteine/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma brucei brucei/drug effects , Trypanosoma brucei rhodesiense/metabolism , Cysteine/analogs & derivatives , Cysteine/chemistry , Cysteine Proteinase Inhibitors/chemical synthesis , Cysteine Proteinase Inhibitors/chemistry , Dose-Response Relationship, Drug , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity Relationship , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistry , Trypanosoma brucei brucei/enzymology
6.
Article in English | MEDLINE | ID: mdl-26072671

ABSTRACT

Synergistic antibacterial activity of combined silver nanoparticles (AgNPs) with tetracycline (polykeptide), neomycin (aminoglycoside), and penicillin (ß-lactam) was tested against the multidrug resistant bacterium Salmonella typhimurium DT104. Dose-dependent inhibition of Salmonella typhimurium DT104 growth is observed for tetracycline-AgNPs and neomycin-AgNPs combination with IC50 of 0.07 µg/mL and 0.43 µg/mL, respectively. There is no inhibition by the penicillin-AgNPs combination. These results suggest that the combination of the ineffective tetracycline or neomycin with AgNPs effectively inhibits the growth of this bacterium. The synergistic antibacterial effect is likely due to enhanced bacterial binding by AgNPs assisted by tetracycline or neomycin, but not by penicillin.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Metal Nanoparticles/chemistry , Salmonella typhimurium/drug effects , Silver/pharmacology , Drug Synergism , Neomycin/pharmacology , Penicillins/pharmacology , Salmonella typhimurium/growth & development , Tetracycline/pharmacology
7.
J Food Drug Anal ; 22(1): 116-127, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24673909

ABSTRACT

Silver is an ancient antibiotic that has found many new uses due to its unique properties on the nanoscale. Due to its presence in many consumer products, the toxicity of nanosilver has become a hot topic. This review summarizes recent advances, particularly the molecular mechanism of nanosilver toxicity. The surface of nanosilver can easily be oxidized by O(2) and other molecules in the environmental and biological systems leading to the release of Ag(+), a known toxic ion. Therefore, nanosilver toxicity is closely related to the release of Ag(+). In fact, it is difficult to determine what portion of the toxicity is from the nano-form and what is from the ionic form. The surface oxidation rate is closely related to the nanosilver surface coating, coexisting molecules, especially thiol-containing compounds, lighting conditions, and the interaction of nanosilver with nucleic acids, lipid molecules, and proteins in a biological system. Nanosilver has been shown to penetrate the cell and become internalized. Thus, nanosilver often acts as a source of Ag(+) inside the cell. One of the main mechanisms of toxicity is that it causes oxidative stress through the generation of reactive oxygen species and causes damage to cellular components including DNA damage, activation of antioxidant enzymes, depletion of antioxidant molecules (e.g., glutathione), binding and disabling of proteins, and damage to the cell membrane. Several major questions remain to be answered: (1) the toxic contribution from the ionic form versus the nano-form; (2) key enzymes and signaling pathways responsible for the toxicity; and (3) effect of coexisting molecules on the toxicity and its relationship to surface coating.


Subject(s)
Metal Nanoparticles/toxicity , Silver , Animals , Cell Membrane/metabolism , DNA Damage , DNA Repair , Humans , Metal Nanoparticles/chemistry , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species/metabolism , Silver/chemistry
8.
Toxicol Ind Health ; 30(6): 489-98, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23012341

ABSTRACT

Water-soluble carbon nanotubes have been found to be one of the most promising nanomaterials in biological- and biomedical-based applications. However, there have been major concerns on their ability to cause cellular and DNA damages upon exposure. In this work, we explore the toxic effects of three multiwalled carbon nanotubes (MWCNTs: nonpurified, purified and carboxylate-functionalized) on human skin keratinocytes (HaCaT). Cytotoxicity tests using the conventional thiazolyl blue tetrazolium bromide (MTT) and the water-soluble tetrazolium (WST-1) assays for 0.5 or 24 h exposure to 20 µg/mL of MWCNTs show that all three caused minimum cytotoxicity that is generally not statistically significant. Assessment of direct and oxidative DNA damages using both alkaline Comet assay and formamidopyrimidine DNA glycosylase-modified Comet assay reveals that the treatment with 20 µg/mL of MWCNTs does not cause significant direct DNA damages, but causes great amount of oxidative DNA damages in HaCaT cells. The oxidative DNA damage reaches the maximum amount at 4 h of incubation in Dulbecco's minimum essential medium, but decreases to the minimum at 8 and 24 h of incubation, indicating repair of the oxidative damages by the intrinsic DNA repair mechanism of the cells.


Subject(s)
DNA Damage/drug effects , Keratinocytes/drug effects , Nanotubes, Carbon/toxicity , Cell Line , Comet Assay , Humans , Oxidative Stress/drug effects , Skin/cytology , Skin/drug effects , Tetrazolium Salts , Thiazoles
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