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Introduction Protein-derived biogenic syntheses of inorganic nanoparticles have gained immense attention because of their broad spectrum of applications. Proteins offer a reducing environment to enable the synthesis of nanoparticles and encapsulate synthesized nanoparticles and provide them temporal stability in addition to biocompatibility. Methods In the present study, Benincasa hispida fruit proteins were used to synthesize silver nanoparticles (AgNPs) at 37 °C over five days of incubation. The synthesis of AgNPs was confirmed by UV-Vis spectroscopy, TEM, zeta potential, and DLS analyses. Further, these NPs depicted antibacterial and antibiofilm effects. Additionally, the anticancer activities of nanoparticles were also tested against the lung cancer cell line (A549) with respect to the normal cell line (NRK) using MTT assay. Further, the estimation of ROS generation through DCFH-DA staining along with a reduction in mitochondrial membrane potential by Mito Tracker Red CMX staining was carried out. Moreover, nuclear degradation in the AgNPs treated cells was cross-checked by DAPI staining. Results The average size of AgNPs was detected to be 27 ±1 nm by TEM analysis, whereas surface encapsulation by protein was determined by FTIR spectroscopy. These NPs were effective against bacterial pathogens such as Escherichia coli, Staphylococcus aureus, Salmonella enteric, and Staphylococcus epidermis with MICs of 148.12 µg/mL, 165.63 µg/mL, 162.77 µg/mL, and 124.88 µg/mL, respectively. Furthermore, these nanoparticles inhibit the formation of biofilms of E. coli, S. aureus, S. enteric, and S. epidermis by 71.14%, 73.89%, 66.66%, and 64.81%, respectively. Similarly, these nanoparticles were also found to inhibit (IC50 = 57.11 µM) the lung cancer cell line (A549). At the same time, they were non-toxic against NRK cells up to a concentration of 200 µM. Discussion We successfully synthesized potentially potent antibacterial, antibiofilm and anticancer biogenic AgNPs., Graphical Abstract

Introduction The use of environmentally benign resources for nanoparticles synthesis is consistently pushed to the front burner in a bid to ensure and enhance environmental protection and beneficiation. In this light, application of different plant parts for the reduction and stabilization of nanoparticles is gaining popularity. Materials and Methods In this contribution, we have exploited Securidaca inappendiculata stem extract (SISE), as the reducing and stabilizing agent for room temperature synthesis of highly stable and dispersed AgNPs. The major bioactive compounds in SISE were profiled using an ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-MS-QTOF-MS). Results and Discussion SISE could reduce silver salts to its nanoparticles almost instantaneously with a maximum absorption spectrum at 423 nm, under the optimal conditions. The fabricated SISE AgNPs was extensively characterized using FTIR, TEM, SEM, XRD, EDS, Zeta analysis/DLS and TGA/DTG analysis. SISE AgNPs with average particles size between 10–15 nm and a zeta potential value of −19.5 ± 1.8 mV was obtained. It was investigated for in-vitro biological applications by carrying out, antimicrobial, antioxidant, hemolytic, cytotoxicity and antidiabetic assays. It was found that SISE AgNPs exhibited potent antimicrobial capacity against some food borne microbes, good antioxidant property, while also demonstrating high biocompatibility. Moreover, with a view to extending further the applications SISE AgNPs, it was tested as a colorimetric nanoprobe for Hg2+ detection in aqueous environment, where good linearity between 0.10 and 10.0 μM, with a detection limit of 26.5 nM, were obtained. The practicality of the probe was investigated by carrying out Hg2+ detection in water sample, with good accuracy and precision. Discussion Overall, this work introduced a new stabilizer for biocompatible AgNPs with far-reaching applications., Graphical Abstract

Heba M Salem,1 Elshaimaa Ismael,2 Mohamed Shaalan3 1Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; 2Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; 3Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, EgyptCorrespondence: Mohamed ShaalanDepartment of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, EgyptTel +20 1151854844Email mohamedibrahim@cu.edu.egBackground: Clostridium perfringens-associated necrotic enteritis (NE) is a serious problem affecting broiler production. A major global challenge is to reduce the use of antibiotics in poultry industry due to their negative impacts on public health. One alternative is to use nanoparticles (NPs) to overcome bacterial resistance to antibiotics. Silver nanoparticles (Ag NPs) showed strong antimicrobial activity.Methods: A total of 120 Cobb broiler chicks (1-day old) were obtained for this study and were divided into 4 equal groups at age of 14 days (30 birds each); each group was subdivided into 3 equal replicates (10 birds each). The groups were designated as follows: G1, infected; G2, infected and treated with Ag NPs; G3, treated with Ag NPs; and G4, negative control. Birds were infected with 4× 108 colony forming unit (CFU)/mL/bird C. perfringens type A for 2 successive days. In the treated groups, Ag NPs (mean diameter 15 nm; total dose 150 μg/bird) were administered via crop gavage. During the observation period (5 weeks), bird performance and immune organ indexes were recorded. Serum samples were collected for immunological evaluation, and tissue samples were collected for histopathology and estimation of Ag NPs residues.Results: Treatment with Ag NPs reduced the colonization of C. perfringens in the intestine and ceca, decreased the severity of clinical signs and reduced mortalities in comparison with infected non-treated group. Ag NPs treatment alleviated pathological lesions in the intestine and liver, but their residues were found in the muscles.Conclusion: Ag NPs have a positive impact on gut health integrity while having no impact on immune organs. Ag NPs have some residues in muscles; therefore, further studies are needed on the concentration and size of Ag NPs, the route of administration, and withdrawal time to ensure the safety of chicken meat for human consumption.Keywords: broiler chickens, Clostridium perfringens, FCR, histopathology, necrotic enteritis, residues, silver nanoparticles

Background Radiotherapy is an important treatment modality for many types of head and neck squamous cell carcinomas. Nanomaterials comprised of high atomic number (Z) elements are novel radiosensitizers enhance radiation injury by production of free radicals and subsequent DNA damage. Gold nanoparticles are upcoming as promising radiosensitizers due to their high (Z) biocompatibility, and ease for surface engineering. Bimetallic nanoparticles have shown enhanced anticancer activity compared to monometallic nanoparticles. Materials and Methods PEG-coated Au–Ag alloy nanoparticles (BNPs) were synthesized using facile one pot synthesis techniques. Size of ~50±5nm measured by dynamic light scattering. Morphology, structural composition and elemental mapping were analyzed by electron microscopy and SAXS (small-angle X-ray scattering). The radiosensitization effects on KB oral cancer cells were evaluated by irradiation with 6MV X-rays on linear accelerator. Nuclear damage was imaged using confocal microscopy staining cells with Hoechst stain. Computed tomography (CT) contrast enhancement of BNPs was compared to that of the clinically used agent, Omnipaque. Results BNPs were synthesized using PEG 600 as reducing and stabilizing agent. The surface charge of well dispersed colloidal BNPs solution was −5mV. Electron microscopy reveals spherical morphology. HAADF-STEM and elemental mapping studies showed that the constituent metals were Au and Ag intermixed nanoalloy. Hydrodynamic diameter was ~50±5nm due to PEG layer and water molecules absorption. SAXS measurement confirmed BNPs size around 35nm. Raman shift of around 20 cm−1 was observed when BNPs were coated with PEG. 1H NMR showed extended involvement of −OH in synthesis. BNPs efficiently enter cytoplasm of KB cells and demonstrated potent in vitro radiosensitization with enhancement ratio ~1.5–1.7. Imaging Hoechst-stained nuclei demonstrated apoptosis in a dose-dependent manner. BNPs exhibit better CT contrast enhancement ability compared to Omnipaque. Conclusion This bimetallic intermix nanoparticles could serve a dual function as radiosensitizer and CT contrast agent against oral cancers, and by extension possibly other cancers as well., Graphical Abstract

Purpose The current study proposed the simple, eco-friendly and cost-effective synthesis of carboxymethyl cellulose (CMC) structured silver-based nanocomposite (CMC-AgNPs) using Syzygium aromaticum buds extract. Methods The CMC-AgNPs were characterized by ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transmission infra-red (FTIR), energy-dispersive X-ray (EDX), and dynamic light scattering (DLS) techniques. The synthesized nanocomposites were evaluated for their bactericidal kinetics, in-vivo anti-inflammatory, anti-leishmaniasis, antioxidant and cytotoxic activities using different in-vitro and in-vivo models. Results The spherical shape nanocomposite of CMC-AgNPs was synthesized with the mean size range of 20–30 nm, and the average pore diameter is 18.2 nm while the mean zeta potential of −31.6 ± 3.64 mV. The highly significant (P < 0.005) antibacterial activity was found against six bacterial strains with the ZIs of 24.6 to 27.9 mm. More drop counts were observed in Gram-negative strains after 10 min exposure with CMC-AgNPs. Significant damage in bacterial cell membrane was also observed in atomic force microscopy (AFM) after treated with CMC-AgNPs. Nanocomposite showed highly significant anti-inflammatory activity in cotton pellet induced granuloma model (Phase I) in rats with the mean inhibitions of 43.13% and 48.68% at the doses of 0.025 and 0.05 mg/kg, respectively, when compared to control. Reduction in rat paw edema (Phase II) was also highly significant (0.025 mg/kg; 42.39%; 0.05 mg/kg, 47.82%). At dose of 0.05 mg/kg, CMC-AgNPs caused highly significant decrease in leukocyte counts (922 ± 83), levels of CRP (8.4 ± 0.73 mg/mL), IL-1 (177.4 ± 21.3 pg/mL), IL-2 (83.7 ± 11.5 pg/mL), IL-6 (83.7 ± 11.5 pg/mL) and TNF-α (18.3 ± 5.3 pg/mL) as compared to control group. CMC-AgNPs produced highly effective anti-leishmaniasis activity with the viable Leishmania major counts decreased up to 36.7% within 24 h, and the IC50 was found to be 28.41 μg/mL. The potent DPPH radical scavenging potential was also observed for CMC-AgNPs with the IC50 value of 112 μg/mL. Furthermore, the cytotoxicity was assessed using HeLa cell lines with the LC50 of 108.2 μg/mL. Conclusion The current findings demonstrate positive attributes of CMC fabricated AgNPs as a promising antibacterial, anti-inflammatory, anti-leishmaniasis, and antioxidant agent with low cytotoxic potential., Graphical Abstract

[Purpose] The importance of studying polyphenolic compounds as natural antioxidants has encouraged the search for new methods of analysis that are quick and simple. The synthesis of silver nanoparticles (AgNPs) using plant extracts has been presented as an alternative to determine the total polyphenolic content and its antioxidant activity., [Methods] In this study, aqueous leaf extract of Solanum mammosum, a species of plant endemic to South America, was used to produce AgNPs. The technique of oxygen radical absorption capacity using fluorescein (ORAC-FL) was used to measure antioxidant activity. The oxidation of the 2´,7´-dichlorodihydrofluorescein diacetate (DCFH2-DA) as fluorescent probe was used to measure cellular antioxidant activity (CAA). Electrochemical behavior was also examined using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Total polyphenolic content (TPH) was analyzed using the Folin-Ciocalteu method, and the major polyphenolic compound was analyzed by high performance liquid chromatography with diode array detector (HPLC/DAD). Finally, a microbial analysis was conducted using Escherichia coli and Bacillus sp., [Results] The average size of nanoparticles was 5.2 ± 2.3 nm measured by high-resolution transmission electron microscopy (HR-TEM). The antioxidant activity measured by ORAC-FL in the extract and nanoparticles were 3944 ± 112 and 637.5 ± 14.8 μM ET/g of sample, respectively. Cellular antioxidant activity was 14.7 ± 0.2 for the aqueous extract and 12.5 ± 0.2 for the nanoparticles. The electrochemical index (EI) was 402 μA/V for the extract and 324 μA/V for the nanoparticles. Total polyphenolic content was 826.6 ± 20.9 and 139.7 ± 20.9 mg EGA/100 g of sample. Gallic acid was the main polyphenolic compound present in the leaf extract. Microbiological analysis revealed that although leaf extract was not toxic for Escherichia coli and Bacillus sp., minor toxic activity for AgNPs was detected for both strains., [Conclusion] It is concluded that the aqueous extract of the leaves of S. mammosum contains nontoxic antioxidant compounds capable of producing AgNPs. The methods using AgNPs can be used as a fast analytical tool to monitor the presence of water-soluble polyphenolic compounds from plant origin. Analysis and detection of new antioxidants from plant extracts may be potentially applicable in biomedicine., This research was funded by the Pontificia Universidad Católica del Ecuador www.puce.edu.ec.

Sandhanasamy Devanesan, Mohamad S AlSalhi Department of Physics and Astronomy, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi ArabiaCorrespondence: Mohamad S AlSalhi Email malsahi@ksu.edu.saBackground: Abelmoschus esculentus (L.) Moench, an economically important malvaceous vegetable crop popularly known as okra, is used in various culinary preparations and is rich in vitamins, minerals, and nutrients. The biological properties of okra flowers in relation to nanoparticle synthesis have not yet been reported.Materials and Methods: In the current study, silver nanoparticles (AgNPs) were synthesized using extracts of the flowers of A. esculentus. The characteristics of the AgNPs were studied using a UV-vis spectrometer, Fourier transmission infrared spectrophotometer (FTIR), X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM) and energy dispersive X-ray spectrometer (EDX). Antibacterial activity screening was performed using the agar well diffusion method, and cytotoxicity and cell viability studies were conducted using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Results: The synthesized AgNPs were spherical and ranged in size from 5.52 to 31.96 nm, with an average size of 16.19 nm, as determined by UV-vis spectroscopy, FTIR, XRD, TEM and EDX. A. esculentus flower extract-mediated silver nanoparticles (AME-AgNPs) exhibited excellent activities in vitro studies, particularly in vitro cytotoxic and antiproliferative studies against cancer cell lines, such as the TERT-4 and A-549 cell lines. The antibacterial effects on the Gram-positive pathogens Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes and the Gram-negative pathogens Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella typhimurium and Shigella sonnei were tested. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values varied with the bacterial strain. The IC50 values of the synthesized NPs for the tested cell lines were close to that of a standard drug.Conclusion: Compared to other NPs the NPs synthesized in this study were smaller in size and exhibited a higher level of antibacterial activity, cytotoxicity and apoptosis at minimal concentrations, and this is the first study on okra flower-induced anticancer and antimicrobial activities.Keywords: Abelmoschus esculentus, silver nanoparticles, okra green pods, cell lines and cytotoxicity

Asmaa M Shehata,1 Fatma MS Salem,1 Eiman M El-Saied,1 Sahar S Abd El-Rahman,2 Mohamed Y Mahmoud,1 Peter A Noshy1 1Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; 2Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, EgyptCorrespondence: Peter A Noshy Email vet_peter@cu.edu.egIntroduction: Silver nanoparticles (Ag-NPs) are among the most commonly used nanoparticles in different fields. Zinc nanoparticles (Zn-NPs) are known for their antioxidant effect. This study was designed to investigate the adverse effects of Ag-NPs (50 nm) on the male reproductive system and also the ameliorative effect of Zn-NPs (100 nm) against these harmful effects.Methods: Forty adult male rats were used in this study; they were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered orally for 90 days.Results: The results revealed that exposure to Ag-NPs adversely affected sperm motility, morphology, viability, and concentration. Ag-NPs also induced oxidative stress and lipid peroxidation in testicular tissue. The exposure to Ag-NPs decreased serum FSH, LH, and testosterone hormones. Additionally, comet assay revealed DNA degeneration in the testicular tissue of rats exposed to Ag-NPs. Histopathological examination showed various histological alterations in the testes of rats intoxicated with Ag-NPs. Furthermore, co-administration of Zn-NPs ameliorated most of the toxic effects of Ag-NPs via their antioxidative capacity.Keywords: antioxidants, DNA damage, endocrinology, oxidative stress, sperm evaluation, testes

The physicochemical and optical properties of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) have allowed them to be employed for various biomedical applications, including delivery, therapy, imaging, and as theranostic agents. However, since they are foreign body systems, they are usually redistributed and accumulated in some vital organs, which can produce toxic effects; therefore, this a crucial issue that should be considered for potential clinical trials. This review aimed to summarize the reports from the past ten years that have used SNPs and GNPs for in vivo studies on the diagnosis and treatment of brain diseases and those related to the central nervous system, emphasizing their toxicity as a crucial topic address. The article focuses on the effect of the nanoparticle´s size and chemical composition as relevant parameters for in vivo toxicity. At the beginning of this review, the general toxicity and distribution studies are discussed separately for SNPs and GNPs. Subsequently, this manuscript analyzes the principal applications of both kinds of nanoparticles for glioma, neurodegenerative, and other brain diseases, and discusses the advances in clinical trials. Finally, we analyze research prospects towards clinical applications for both types of metallic nanoparticles.

Dan Yu,1,2,* Qilong Yin,1,3,* Jiwei Wang,1,* Jian Yang,1 Zimeng Chen,1 Zihan Gao,1 Qingli Huang,1,4 Shibao Li1,3 1Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 4Public Experimental Research of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingli HuangPublic Experimental Research of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaTel +86 15150043097Fax +86 516 83262091Email qlhuang@xzhmu.edu.cnShibao LiDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaTel +86 15895212960Fax +86 516 83353651Email sdjnshlb@xzhmu.edu.cnPurpose: Developing a sensitive SERS-based method to quantitatively detect serum biomarkers (Aβ 1-42 and P-Tau-181) for the early diagnosis of Alzheimer’s disease (AD).Methods: In this study, a novel SERS-based sandwich immunoassay, which consists of tannin-capped silver nanoparticles and magnetic graphene oxide (Fe3O4@GOs), was developed. We firstly applied this method for the detection of protein standards in buffer solution, obtaining the regression equation. Then, its potential value on real serum samples of AD was further explored.Results: The detection linear range of Aβ 1-42 and P-Tau-181 protein standards were observed to range from 100 pg mL− 1 to 10 fg mL− 1, 100 pg mL− 1 to 1 fg mL− 1 respectively. We finally explored clinical application of the proposed method in 63 serum samples. As a result, P-tau-181 differentiated AD from non-AD dementia patients (AUC = 0.770), with a more favored ROC than Aβ 1-42 (AUC =  0.383).Conclusion: The developed SERS-based immunoassay is successfully applied to the determination of Aβ 1-42 and P-Tau-181 in human serum specimens, which provides a promising tool for the early diagnosis of AD.Keywords: surface-enhanced Raman scattering, silver probe, Alzheimer’s disease, biomarker, diagnosis

Moran Huang,1,* Kai Ye,1,* Tu Hu,2,* Kexin Liu,3 Mengzhen You,3 Lei Wang,1 Hui Qin1 1Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of General Practice, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Qin; Lei WangDepartment of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, No. 600 Yishan Road, Shanghai, People’s Republic of ChinaTel +86-135-64143033; +86-189-30172609Fax +8621-6470-1361Email qh197826@163.com; wanglei2264@126.comPurpose: Despite the extensive development of antibacterial biomaterials, there are few reports on the effects of materials on the antibacterial ability of the immune system, and in particular of neutrophils. In this study, we observe differences between the in vivo and in vitro anti-infective efficacies of silver nanoparticles (AgNPs). The present study was designed to further explore the mechanism for this inconsistency using ex vivo models and in vitro experiments.Methods: AgNPs were synthesized using the polyol process and characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. The antibacterial ability of AgNPs and neutrophils was tested by the spread-plate method. The infected air pouch model was prepared to detect the antimicrobial ability of AgNPs in vivo. Furthermore, blood-AgNPs-bacteria co-culture model and reactive oxygen species (ROS) measurement were used to evaluate the effect of AgNPs to neutrophil-mediated phagocytosis and ROS production.Results: The antibacterial experiments in vitro showed that AgNPs had superior antibacterial properties in cell compatible concentration. While, AgNPs had no significant antibacterial effect in vivo, and pathological section in AgNPs group indicated less neutrophil infiltration in inflammatory site than S. aureus group. Furthermore, AgNPs were found to reduce the phagocytosis of neutrophils and inhibit their ability to produce ROS and superoxide during ex vivo and in vitro experiments.Conclusion: This study selects AgNPs as the representative of inorganic nano-biomaterials and reveals the phenomenon and the mechanism underlying the significant AgNPs-induced inhibition of the antibacterial ability of neutrophils, and may have a certain enlightening effect on the development of biomaterials in the future. In the fabrication of antibacterial biomaterials, however, attention should be paid to both cell and immune system safety to make the antibacterial properties of the biomaterials and innate immune system complement each other and jointly promote the host’s ability to resist the invasion of pathogenic microorganisms.Keywords: antibacterial biomaterials, polymorphonuclear neutrophils, silver nanoparticles, immune system

Jayanta Kumar Patra,1 Han-Seung Shin,2 Gitishree Das1 1Research Institute of Biotechnology & Medical Converged Science, Dongguk University-Seoul, Gyeonggi-do, 10326, Republic of Korea; 2Department of Food Science and Biotechnology, Dongguk University‐Seoul, Gyeonggi‐do, 10326, Republic of KoreaCorrespondence: Gitishree DasResearch Institute of Biotechnology & Medical Converged Science, Dongguk University-Seoul, Gyeonggi-do, 10326, Republic of KoreaEmail gitishreedas@gmail.comBackground: The dragon tongue beans are a legume belonging to the Fabaceae family, are rich in protein, starch, fiber, and other micronutrients that have numerous health-promoting benefits. Its peel commonly the waste parts also contains lots of bioactive compounds.Materials and Methods: In the current research, dragon tongue bean peels (DtbP) extract is tested for the existence of phytochemicals. Ag nanoparticles are biosynthesized using DtbP extract. The generated DtbP silver nanoparticle characterization was accomplished using UV-Vis spectral analysis, FTIR spectral analysis, SEM analysis, EDX analysis, XRD analysis, zeta potential, and DLS study. Furthermore, comparative assessment on multi-biological activities of the biosynthesized Ag nanoparticles was accomplished by employing cytotoxicity (inhibition against HepG2 cancer cells), antidiabetic (α-glucosidase inhibition assay), and antioxidant (free-radical scavenging) analysis.Results: The characterization result of the DtbP-AgNPs demonstrated that the AgNPs synthesized within 24 h. The AgNPs are nearly spherical. The biological effect assay of AgNPs displayed that DtbP-AgNPs is having significant cytotoxicity, antidiabetic, and moderate antioxidant effect. This study results as a whole report the biosynthesis of DtbP-AgNPs utilizing the legume dragon tongue bean waste peel and assessment of their multiple biological activities. The synthesized DtbP-AgNPs could serve as a potential candidate in the pharmaceutical industries in the formulation of drugs for the treatment of several medical ailments concerning cancer, diabetes, etc.Keywords: antidiabetic, antioxidant, cytotoxicity, legume peel, silver nanoparticles, green nano-synthesis

Shan Hu,1– 3,* Haiquan Kang,4,* Feng Gu,2,* Chongwen Wang,1,5 Siyun Cheng,3 Wenjing Gong,1 Liping Wang,1 Bing Gu,3,4 Ying Yang1 1Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, 100850, People’s Republic of China; 2Department of Laboratory Medicine, Xuzhou Tumor Hospital, Xuzhou, 221005, People’s Republic of China; 3Xuzhou Key Laboratory of Laboratory Diagnostics, Medical Technology School of Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 4Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China; 5College of Life Sciences, Anhui Agricultural University, Hefei, 230036, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Yang; Bing Gu Email y_ying_77@163.com; gb20031129@163.comPurpose: Candidemia infection is common in the clinic and has a high mortality rate. Candida albicans, Candida tropicalis, and Candida krusei are very important and common pathogenic species. Candida is difficult to isolate from clinical samples and culture, and immunological detection cannot distinguish these related strains. Furthermore, Candida has a complex cell wall, which causes difficulties in the extraction of DNA for nucleic acid detection. The purpose of this study was to establish a protocol for the direct identification of Candida from serum.Materials and Methods: We synthesized Fe3O4@PEI (where PEI stands for polyethylenimine) magnetic nanoparticles to capture Candida and prepared positively charged silver nanoparticles (AgNPs+) as the substrate for surface-enhanced Raman scattering (SERS). Candida was directly identified from serum by SERS detection.Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) was used as the multivariate analysis tool. Principal component analysis confirmed that this method can clearly distinguish common Candida. After 10-fold cross-validation, the accuracy of training data in this model was 100% and the accuracy of test data was 99.8%, indicating that the model has good classification ability.Conclusion: The detection could be completed within 40 minutes using Fe3O4@PEI and AgNPs+ prepared in advance. This is the first time that Fe3O4@PEI was used in the detection of Candida by SERS. We report the first rapid method to identify fungi directly from serum without breaking the cell wall to extract DNA from the fungi.Keywords: capture, surface-enhanced Raman scattering, positively charged silver nanoparticles, orthogonal partial least squares discriminant analysis, 10-fold cross-validation

Reham Samir Hamida,1 Mohamed Abdelaal Ali,2 Doaa A Goda,3 Mayasar Ibrahim Al-Zaban4 1Molecular Biology Unit, Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt; 2Biotechnology Unit, Department of Plant Production, College of Food and Agriculture Science, King Saud University, Riyadh, Saudi Arabia; 3Bioprocess Development Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), Alexandria, Egypt; 4Department of Biology, College of Science Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaCorrespondence: Mohamed Abdelaal Ali Email mali3@ksu.edu.saMayasar Ibrahim Al-Zaban Email Mialzaban@pnu.edu.saBackground: Increasing antibiotic resistance and the emergence of multidrug-resistant (MDR) pathogens have led to the need to develop new therapeutic agents to tackle microbial infections. Nano-antibiotics are a novel generation of nanomaterials with significant antimicrobial activities that target bacterial defense systems including biofilm formation, membrane permeability, and virulence activity.Purpose: In addition to AgNO3, the current study aimed to explore for first time the antibacterial potential of silver nanoparticles synthesized by Nostoc sp. Bahar_M (N-SNPs) and their killing mechanisms against Streptococcus mutans, methicillin-resistant Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium.Methods: Potential mechanisms of action of both silver species against bacteria were systematically explored using agar well diffusion, enzyme (lactate dehydrogenase (LDH) and ATPase) andantioxidant (glutathione peroxidase and catalase) assays, and morphological examinations. qRT-PCR and SDS-PAGE were employed to investigate the effect of both treatments on mfD, flu, and hly gene expression and protein patterns, respectively.Results: N-SNPs exhibited greater biocidal activity than AgNO3 against the four tested bacteria. E. coli treated with N-SNPs showed significant surges in LDH levels, imbalances in other antioxidant and enzyme activities, and marked morphological changes, including cell membrane disruption and cytoplasmic dissolution. N-SNPs caused more significant upregulation of mfD expression and downregulation of both flu and hly expression and increased protein denaturation compared with AgNO3.Conclusion: N-SNPs exhibited significant inhibitory potential against E. coli by direct interfering with bacterial cellular structures and/or enhancing oxidative stress, indicating their potential for use as an alternative antimicrobial agent. However, the potential of N-SNPs to be usable and biocompatible antibacterial drug will evaluate by their toxicity against normal cells.Keywords: biological synthesis, nanoparticles, pathogenic bacteria, Nostoc sp. Bahar_M, silver, antibacterial activity

Ajeet Kumar, 1 Dan V Goia 2 1Ames Electronic Materials Division, South Plainfield, NJ 07080, USA; 2Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13676, USACorrespondence: Dan V GoiaDepartment of Chemistry and Biomolecular Science, 123 Science Center, 8 Clarkson Ave, Potsdam, NY 13699, USATel +1 315 268 4411Email dgoia@clarkson.eduPurpose: The public fear associated with the novel coronavirus (SARS-CoV-2) pandemic has triggered recently a significant proliferation of supplements touted as potential cures against bacteria and viruses. Colloidal silver has particularly benefited from this rush given its empirically and scientifically documented anti-bacterial and anti-viral actions. The lack of standards in the unregulated supplements industry remains a major roadblock in evaluating the quality and consistency of marketed products or assessing the accuracy of the information provided by manufacturers. This study is the first scientifically rigorous attempt to evaluate commercial silver colloidal products offered for sale on the internet.Methods: Fourteen of the most popular colloidal silver products purchased from Amazon (www.amazon.com) were evaluated using state-of-the-art analytical techniques widely accepted as gold standards for investigating the properties (size, shape) and the dispersion of silver nanoparticles.Results: Commercial samples were analysed using UV-Vis, FE-SEM and AAS techniques. In general, the Ag concentration was very close to those claimed by the manufacturer. The colorless product shows no absorbance in the UV-Vis analysis. The FESEM and STEM images confirmed the conclusions of the UV-Vis analysis.Conclusion: The results of this evaluation show clearly that 70% of the commercial products evaluated contain only ionic silver. Despite the evidence showing that silver nanoparticles are not present, eight of these products are promoted by the manufacturers as ‘colloidal silver’. Considering the extensive scientific research showing major differences between silver ionic and silver nanoparticles in terms of mechanisms of action, efficacy and safety, it is clear that this misrepresentation impacts the consumers and must be addressed. This study serves as blueprint for a scientific protocol to be followed by manufacturers for characterizing their silver supplements.Keywords: colloidal silver, nanodispersion, bio-active, supplement, antimicrobial, UV-Vis analysis

Background The natural food waste peels/shells discarded as waste materials are ample sources of natural bioactive compounds. The natural food waste mediated silver (Ag) nanoparticle (NPs) synthesis will be advantageous over chemical synthesis. Materials and methods Using the various phytochemical-rich ripe P. americana peel (PAP), fresh Beta vulgaris peel (BVP), and rawArachis hypogaea shell (AHS) extracts, the bio-synthesis of PAP-AgNPs, BVP-AgNPs, and AHS-AgNPs, respectively, were carried out and its characterization was completed by standard procedures. The three biosynthesized AgNP's multiple biological effects were accomplished by evaluating their cytotoxicity, antidiabetic, and antioxidant effects. Results The biosynthesis of the three generated Ag nanoparticles was confirmed through UV-vis spectrum analysis while the X-ray diffraction outlines revealed the generated AgNPs nature. The morphological structure and elemental information of the three AgNPs were obtained through SEM (scanning electron microscopy) and EDX (energy-dispersive X-ray) study. Multiple biological assays exhibited that the three generated AgNPs have significant cytotoxic, antidiabetic, and moderate antioxidant activity. In a comparative analysis, the PAP-AgNPs displayed higher anticancer potential than BVP and AHS-AgNPs, whereas AHS-AgNPs exhibited a higher antidiabetic effect with the lowest IC50 value (1.68 µg/mL) than PAP and BVP AgNPs. All three generated AgNPs displayed moderate antioxidant effects, among them BVP-AgNPs were more effective than PAP and AHS AgNPs. More than two effects of the three biosynthesized AgNPs specifies that they have ample perspective in therapeutic applications in pharmaceutical and other related industries in controlling cancer and diabetes.

Introduction We report, herein, in vitro, and in vivo toxicity evaluation of silver nanoparticles stabilized with gum arabic protein (AgNP-GP) in Daphnia similis, Danio rerio embryos and in Sprague Dawley rats. Purpose The objective of this investigation was to evaluate in vitro and in vivo toxicity of silver nanoparticles stabilized with gum arabic protein (AgNP-GP), in multispecies due to the recognition that toxicity evaluations beyond a single species reflect the environmental realism. In the present study, AgNP-GP was synthesized through the reduction of silver salt using the tri-alanine-phosphine peptide (commonly referred to as "Katti Peptide") and stabilized using gum arabic protein. Methods In vitro cytotoxicity tests were performed according to ISO 10993-5 protocols to assess cytotoxicity index (IC50) values. Acute ecotoxicity (EC50) studies were performed using Daphnia similis, according to the ABNT NBR 15088 protocols. In vivo toxicity also included evaluation of acute embryotoxicity using Danio rerio (zebrafish) embryos following the OECD No. 236 guidelines. We also used Sprague Dawley rats to assess the toxicity of AgNP-GP in doses from 2.5 to 10.0 mg kg-1 body weight. Results AgNP-GP nanoparticles were characterized through UV (405 nm), core size (20±5 nm through TEM), hydrodynamic size (70-80 nm), Zeta (ζ) potential (- 26 mV) using DLS and Powder X ray diffraction (PXRD) and EDS. PXRD showed pattern consistent with the Ag (1 1 1) peak. EC50 in Daphnia similis was 4.40 (3.59-5.40) μg L-1. In the zebrafish species, LC50 was 177 μg L-1. Oral administration of AgNP-GP in Sprague Dawley rats for a period of 28 days revealed no adverse effects in doses of up to 10.0 mg kg-1 b.w. in both male and female animals. Conclusion The non-toxicity of AgNP-GP in rats offers a myriad of applications of AgNP-GP in health and hygiene for use as antibiotics, antimicrobial and antifungal agents.

Background The application of silver nanoparticles (AgNPs) is growing exponentially, and its potential damage to the cardiac remains to be elucidated. The purpose of this study was to investigate the ameliorative effect of sodium selenite on silver nanoparticles-induced myocardiocyte structural alterations in rats. Materials and Methods Forty male Sprague-Dawley (SD) rats were randomly divided into four groups: control group, AgNPs group, Se control group, and AgNPs + Se group. SD rats were administered AgNPs through a single intratracheal instillation, and sodium selenite was given by intraperitoneal injection for seven days. Cardiac function was determined by echocardiography and hemodynamic, ultrastructural changes by transmission electron microscopy examination. Mitochondrial fission and autophagy markers were measured by Western blotting. Results AgNPs caused a significant decrease in cardiac contraction, diastolic dysfunction, fragmentation, and lysis of the myofibrils, the formation of stenosis in the capillary, damaging the mitochondria membrane and cristae. AgNPs significantly increased mitochondrial fission markers dynamin-related protein 1 (Drp1), phospho-Drp1 (p-Drp1), and mitochondrial fission protein 1 (Fis1), as well as autophagy marker LC3 II/I (P

Background The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer's onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. Objective The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. Methods The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11-7082. Results The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381-452 nm wherein the particles size ranged between 19.2±0.1 to 220.77±0.12 nm with the charge range -9.99±0.8 to -34.63±0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. Conclusion This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.

Muhammad Arif Asghar,1 Rabia Ismail Yousuf,1 Muhammad Harris Shoaib,1 Muhammad Asif Asghar,2 Sabah Ansar,3 Mehrukh Zehravi,4 Ahad Abdul Rehman5 1Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan; 2Food and Feed Safety Laboratory, Food and Marine Resources Research Centre, PCSIR Laboratories Complex, Karachi, Sindh 74200, Pakistan; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia; 4Department of Clinical Pharmacy, College of Pharmacy for Girls, Prince Sattam Bin Abdul Aziz University, Al-Kharj 16278, Kingdom of Saudi Arabia; 5Department of Pharmacology, Faculty of Pharmacy, Jinnah Sindh Medical University, Karachi 75510, PakistanCorrespondence: Rabia Ismail Yousuf; Muhammad Harris ShoaibDepartment of Pharmaceutics and Bioavailability and Bioequivalence Research Facility, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, PakistanEmail rabia_pharmaceutics@yahoo.com; harrisshoaib2000@yahoo.comPurpose: The present study reports chitosan functionalized green synthesized CS-AgNPs, conjugated with amoxicillin (AMX), cefixime (CEF), and levofloxacin (LVX) for safe and enhanced antibacterial activity.Methods: The CS-AgNPs and conjugates CS-AgNPs+AMX CS-AgNPs+CEF, and CS-AgNPs+LVX were characterized by UV–Vis, FTIR, SEM, TEM, EDX spectroscopy. The size distribution and zeta potential were measured using the dynamic light scattering (DLS) technique. The interaction between CS-AgNPs and antibiotic molecules was also investigated using UV–Vis spectroscopy at the concentrations of 5, 50, 500, and 5000 μM for each antibiotic. Antibacterial activity and synergism were assessed by the Fractional Inhibitory Concentration (FIC) index. The mechanism for synergistic activity was investigated by the detection of hydroxyl species based on the chemiluminescence of luminol. The biocompatibility index (BI) was calculated from IC50 using the HeLa cell line. In vivo toxicity and tissue distribution of silver ions were evaluated on Sprague Dawley rats. Physical interactions of antibiotics and significant (P< 0.05) antibacterial activity were observed after loading on CS-AgNPs surfaces.Results: The spherical shape nanocomposites of CS-AgNPs with different antibiotics were prepared with mean size ranges of 80– 120 nm. IC50 of antibiotics-conjugated CS-AgNPs decreased compared to CS-AgNPs. The biocompatibility (BI) index showed that antibiotics-conjugated CS-AgNPs have high antibacterial potential and low toxicity. Highly significant (P< 0.005) increase in the generation of hydroxyl species indicated the radical scavenging mechanism for synergistic activity of CS-AgNPs after combined with different antibiotics. Biochemical analysis and histopathological examinations confirmed low toxicity with minor hepatotoxicity at higher doses. After oral administration, extensive distribution of Ag ion was observed in spleen and liver.Conclusion: The study demonstrates positive attributes of antibiotics-conjugated CS-AgNPs, as a promising antibacterial agent with low toxicity.Keywords: chitosan functionalized silver nanoparticles, antibiotic resistance, synergistic antibacterial activity, in vivo toxicity, tissue distribution

Background Metallic nanoparticles (NPs) are highly exploited in manufacturing and medical processes in a broad spectrum of industrial applications and in the academic sectors. Several studies have suggested that many metallic nanomaterials including those derived by silver (Ag) are entering the ecosystem to cause significant toxic consequences in cell culture and animal models. However, ecotoxicity studies are still receiving limited attention when designing functionalized and non.-functionalized AgNPs. Objective This study aimed to investigate different ecotoxicological profiles of AgNPs, which were analyzed in two different states: in pristine form uncoated AgNPs and coated AgNPs with the antimicrobial peptide indolicidin. These two types of AgNPs are exploited for a set of different tests using Daphnia magna and Raphidocelis subcapitata, which are representatives of two different levels of the aquatic trophic chain, and seeds of Lepidium sativum, Cucumis sativus and Lactuca sativa. Results Ecotoxicological studies showed that the most sensitive organism to AgNPs was crustacean D. magna, followed by R. subcapitata and plant seeds, while AgNPs coated with indolicidin (IndAgNPs) showed a dose-dependent decreased toxicity for all three. Conclusion The obtained results demonstrate that high ecotoxicity induced by AgNPs is strongly dependent on the surface chemistry, thus the presence of the antimicrobial peptide. This finding opens new avenues to design and fabricate the next generation of metallic nanoparticles to ensure the biosafety and risk of using engineered nanoparticles in consumer products.

Purpose In this study, silver nanoparticles (AgNPs) were biosynthesized using culture supernatant of strain Shewanella sp. ARY1, characterized and their antibacterial activity was investigated against Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae. Methods The strain Shewanella sp. ARY1 was isolated from river Yamuna, Delhi and used for biosynthesis of AgNPs via extracellular approach. Biosynthesized AgNPs were characterized by UV-Visible (UV-Vis) spectrophotometer, fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), energy dispersive X-ray (EDX), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Antibacterial activity of AgNPs was determined by well diffusion, broth microdilution and streaking plate assay to determine the zone of inhibition (ZOI), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), respectively. The effect of AgNPs on treated bacteria was investigated by electron microscopy analysis. Further, the biocompatibility of AgNPs was tested against mice erythrocytes (RBC) by hemolytic assay. Results The UV-Vis spectral analysis revealed absorption maxima at 450 nm which confirmed the formation of AgNPs. The FTIR analysis suggested the involvement of various supernatant biomolecules, as reducing and capping agents in the synthesis of AgNPs. The XRD and EDX analysis confirmed the crystalline and metallic nature of AgNPs, respectively. The TEM and SEM analysis showed nanoparticles were spherical with an average size of 38 nm. The biosynthesized AgNPs inhibited the growth and formed a clear zone of inhibition (ZOI) against tested Gram-negative strains. The MIC and MBC were determined as 8-16 µg/mL and 32 µg/mL, respectively. Further, electron microscopy analysis of treated cells showed that AgNPs can damage the outer membrane, release of cytoplasmic contents, and alter the normal morphology of Gram-negative bacteria, leading to cell death. The hemolytic assay indicated that the biosynthesized AgNPs were biocompatible at low dose concentrations. Conclusion This study demonstrates an eco-friendly process for extracellular synthesis of AgNPs using Shewanella sp. ARY1 and these AgNPs exhibited excellent antibacterial activity, which may be used to combat Gram-negative pathogens.

Background With excellent shape memory and superelastic properties, shape memory alloy (SMA) is an ideal actuator, and it can form smart structure for different applications in medical field. However, SMA devices cause apparent thermal damage to the surrounding tissues when it works in vivo, making the application of smart structure that is composed of SMA actuator in vivo is greatly limited. Methods In this paper, coating (APA) with PLA as the main body to limit the heat conduction, a multifunctional Ag nanoparticles (AgNPs)/polylactic acid (PLA)/Al2O3 was synthesized. The Al2O3 layer was formed by micro-arc oxidation (MAO) and AgNPs were synthesized by silver nitrate and ethylene glycol. Scanning electron microscopy, transmission electron microscope, and Fourier transform infrared spectra were applied to analyze the morphology and characterization of APA coating. The antimicrobial activity, thermal insulation activity, and biocompatibility of APA coating were furtherly explored and verified through animal experiments and immunohistochemistry. Results With different particle sizes and concentrations of AgNPs, APA multi-functional films were successfully prepared. The Al2O3 layer was closely combined with SMA and formed a porous surface, so the PLA and AgNPs layers can firmly adhere to SMA, thus reducing the release of nickel ions in SMA. AgNPs gave APA coating excellent antibacterial activity and effectively inhibited the growth of Staphylococcus aureus. In addition, coupled with the low thermal conductivity of PLA and Al2O3, AgNPs were tightly anchored on the surface of PLA, which has high infrared reflectivity, making the APA coating obtain good thermal insulation performance. Conclusion We have successfully prepared the APA coating and obtained the optimum amount of AgNPs, which makes it have good thermal insulation performance, good antibacterial activity and good biocompatibility, which provides a new prospect for the application of SMA.

Introduction Silver nanoparticles (AgNPs) have been extensively used in wound healing applications owing to their valuable physicochemical and biological properties. The main objective of this study was to evaluate the combined effects of green-synthesized silver nanoparticles (G-AgNPs) and photobiomodulation (PBM; laser irradiation at 830 nm with 5 J/cm2) in normal wounded and diabetic wounded fibroblast cells (WS1). Methods The combined effect of G-AgNPs and PBM was studied by various in vitro wound healing studies including cell morphology, cell migration rate and percentage wound closure, cell viability, cell proliferation, and filamentous (F)-actin and nuclear morphology staining. Results Cell viability results revealed good cellular compatibility of G-AgNPs to WS1 cells. The combined therapy of G-AgNPs and PBM demonstrated promising results to achieve progressive migration and wound closure in both normal wounded and diabetic wounded cell models. G-AgNPs alone and in combination with PBM had no negative effect on cell viability and proliferation, and there was an increase in cell migration. Conclusion Overall, these findings demonstrate that the combined treatment of G-AgNPs and PBM does not display any adverse effects on wound healing processes in both normal wounded and diabetic wounded cell models.

Background In the last decades, nosocomial infections caused by drug-resistant Pseudomonas aeruginosa became a common problem in healthcare facilities. Antibiotics are becoming less effective as new resistant strains appear. Therefore, the development of novel enhanced activity antibacterial agents becomes very significant. A combination of nanomaterials with different physical and chemical properties enables us to generate novel multi-functional derivatives. In this study, graphene oxide and polyvinylpyrrolidone-stabilized silver nanoparticles hybrid nanocomposite (GO-Ag HN) were synthesized. The relation between antibiotic resistance and GO-Ag HN potential toxicity to clinical P. aeruginosa strains, their antibiotic resistance, and molecular mechanisms were assessed. Methods Chemical state, particle size distribution, and morphology of synthesized GO-Ag NH were investigated using spectroscopy and microscopy techniques (UV-Vis, FTIR, XPS, TEM, SEM, AFM). Broad-spectrum antibiotic resistance of P. aeruginosa strains was determined using E-test. Antibiotic resistance genes were identified using polymerase chain reaction (PCR). Results In this study, the toxicity of the GO-Ag NH to the isolated clinical P. aeruginosa strains has been investigated. A high antibiotic resistance level (92%) was found among P. aeruginosa strains. The most prevalent antibiotic resistance gene among tested strains was the AMPC beta-lactamase gene (65.6%). UV-vis, FTIR, and XPS studies confirmed the formation of the silver nanoparticles on the GO nanosheets. The functionalization process occurred through the interaction between Ag nanoparticles, GO, and polyvinylpyrrolidone used for nanoparticle stabilization. SEM analysis revealed that GO nanosheets undergo partial fragmentation during hybrid nanocomposite preparation, which remarkably increases the number of sharp edges and their mediated cutting effect. TEM analysis showed that GO-Ag HN spherical Ag nanoparticles mainly 9-12 nm in size were irregularly precipitated on the GO nanosheet surface. A higher density of Ag NPs was observed in the sheets' wrinkles, corrugations, and sharp edges. This hybrid nanocomposite poses enhanced antibacterial activity against carbapenem-resistant P. aeruginosa strains through a possible synergy between toxicity mechanisms of GO nanosheets and Ag nanoparticles. With incubation time increasing up to 10 minutes, the survival of P. aeruginosa decreased significantly. Conclusion A graphene oxide and silver nanoparticles hybrid composite has been shown to be a promising material to control nosocomial infections caused by bacteria strains resistant to most antibiotics.

Purpose Indocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy. Methods and results PEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG ("PEG-BSA-AgNP/ICG"). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity. Conclusion Our findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.

Background Bactericidal capacity, durable inhibition of biofilm formation, and a three-dimensional (3D) porous structure are the emphases of infected bone defect (IBD) treatment via local scaffold implantation strategy. Purpose In this study, silver nanoparticle (AgNP)-loaded nano-hydroxyapatite (nHA)@ reduced graphene oxide (RGO) 3D scaffolds (AHRG scaffolds) were designed to alleviate bone infection, inhibit biofilm formation, and promote bone repair through the synergistic effects of AgNPs, RGO, and nHA. Materials and methods AHRGs were prepared using a one-step preparation method, to create a 3D porous scaffold to facilitate a uniform distribution of AgNPs and nHA. Methicillin-resistant Staphylococcus aureus (MRSA) was used as a model-resistant bacterium, and the effects of different silver loadings on the antimicrobial activity and cytocompatibility of materials were evaluated. Finally, a rabbit IBD model was used to evaluate the therapeutic effect of the AHRG scaffold in vivo. Results The results showed successful synthesis of the AHRG scaffold. The ideal 3D porous structure was verified using scanning electron microscopy and transmission electron microscopy, and X-ray photoelectron spectroscopy and selected area electron diffraction measurements revealed uniform distributions of AgNP and nHA. In vitro antibacterial and cytocompatibility indicated that the 4% AHRG scaffolds possessed the most favorable balance of bactericidal properties and cytocompatibility. In vivo evaluation of the IBD model showed promising treatment efficacy of AHRG scaffolds. Conclusion The as-fabricated AHRG scaffolds effectively eliminated infection and inhibited biofilm formation. IBD repair was facilitated by the bactericidal properties and 3D porous structure of the AHRG scaffold, suggesting its potential in the treatment of IBDs.

Purpose The present study synthesized silver nanoparticles (AgNPs) using the aqueous extract of a traditional medicinal product consisting of an oleoresin (a combination of macromolecules of carbohydrates and proteins) exuded from the rhizome of the plant Ferula foetida (asafoetida gum) and evaluated its biological properties. Materials and methods The silver nanoparticles synthesized using asafoetida gum (As-AgNPs) were characterized using UV/Vis spectroscopy, fourier infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM) and EADX. The cytotoxicity and antimicrobial activity As-AgNPs were evaluated against MCF-7 cell lines and selected microbial pathogens, respectively. Results The synthesized silver nanoparticles were crystalline in nature with a spherical shape. The average particle size was 5.6-8.6 nm. The cytotoxicity of the synthesized As-AgNPs was evaluated against MCF-7 cell lines, and the As-AgNPs were found to be effective in inhibiting the multiplication of cancer cells. The As-AgNPs exhibited significant antimicrobial activity towards E. coli, K. pneumoniae and C. albicans. The MIC of the synthesized As-AgNPs was 7.80 μg/mL for E. coli ATCC 25922, Salmonella sp. WS50- and S. typhi; 15.60 μg/mL for S. typhimurium and S. aureus WS10, and 31.20 μg/mL for K. pneumoniae and S. aureus ATCC 43300-MRSA. In addition, MIC values of 15.60 μg/mL for C. albicans ATCC8436 and 31.20 μg/mL for C. krusei ATCC6258 were obtained. Conclusion As asafoetida is a good traditional medicine, its involvement in the synthesis of AgNPs led the silver nanoparticles to exhibit good cytotoxic and antimicrobial effects.

Purpose: Selenium nanoparticles (Se NPs) are promising antibacterial agents to tackle the growing problem of antimicrobial resistance. The aim of this study was to fabricate Se NPs with a net positive charge to enhance their antibacterial efficacy. Methods: Se NPs were coated with a positively charged protein--recombinant spider silk protein eADF4([kappa] 16)--to give them a net positive surface charge. Their cytotoxicity and antibacterial activity were investigated, with negatively charged polyvinyl alcohol coated Se NPs as a control. Besides, these eADF4([kappa] 16)-coated Se NPs were immobilized on the spider silk films, and the antibacterial activity of these films was investigated. Results: Compared to the negatively charged polyvinyl alcohol coated Se NPs, the positively charged eADF4([kappa] 16)-coated Se NPs demonstrated a much higher bactericidal efficacy against the Gram-negative bacteria E. coli, with a minimum bactericidal concentration (MBC) approximately 50 times lower than that of negatively charged Se NPs. Cytotoxicity testing showed that the eADF4([kappa] 16)-coated Se NPs are safe to both Balb/3T3 mouse embryo fibroblasts and HaCaT human skin keratinocytes up to 31 [micro]g/mL, which is much higher than the MBC of these particles against E. coli (8 [+ or -] 1 [micro]g/mL). In addition, antibacterial coatings were created by immobilising the eADF4([kappa] 16)-coated Se NPs on positively charged spider silk films and these were shown to retain good bactericidal efficacy and overcome the issue of low particle stability in culture broth. It was found that these Se NPs needed to be released from the film surface in order to exert their antibacterial effects and this release can be regulated by the surface charge of the film, such as the change of the spider silk protein used. Conclusion: Overall, eADF4([kappa] 16)-coated Se NPs are promising new antibacterial agents against life-threatening bacteria.

Purpose Paclitaxel is a generic drug produced based on Taxol which is an extract of Taxus tree, well known for its anticancer and antibacterial effects. This study was aimed at building up an agent with the antibacterial and anticancer benefits of both the silver ions and Taxol, together with less cytotoxic effects. Materials and methods Colloidal silver nanoparticles (AgNPs) were synthesized by reducing aqueous AgNO3 with aqueous Taxus leaf extract at nonphotomediated conditions, without any catalyst, template or surfactant. The AgNP production was confirmed by ultraviolet-visible (UV-VIS) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier-transform infrared (FTI) spectroscopy. The MTT assay for human breast cancer cells as well as the DAPI fluorescent staining microscopy tested the biocompatibility and anticancer effects of AgNPs, silver nitrate, and Taxol. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques were performed to determine the shape and size of the nanoparticles. MTT assay showed the best inhibitory concentration of AgNPs on cancer cells. The antibacterial activity of the three case study materials was tested for gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using well diffusion test. Results This work proposes more anticancer effects for AgNP made by Taxus brevifolia extract, comparing Taxol solution. IC50 was observed as 3.1 mM for Taxol while 1.5 mM for new AgNP. Moreover, Taxus showed no antibacterial effects while the new AgNP showed a dose-dependent biocompatibility along with slightly more antibacterial effects (MIC: 1.6 and 6.6mM for gram-positive and -negative bacteria, respectively) comparing with silver nitrate solution (MIC: 1.5 and 6.2 mM for gram-positive and -negative bacteria, respectively). Conclusion The production of herbal-mediated silver nanoparticles may be an efficient substitution for the silver nitrate-based medicines with less side effects.

Background: Hepatitis C virus (HCV) infection is a major cause of hepatic diseases all over the world. This necessitates the need to discover novel anti-HCV drugs to overcome emerging drug resistance and liver complications. Purpose: Total extract and petroleum ether fraction of the marine sponge (Amphimedon spp.) were used for silver nanoparticle (SNP) synthesis to explore their HCV NS3 helicase-and protease-inhibitory potential. Methods: Characterization of the prepared SNPs was carried out with ultraviolet-visible spectroscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. The metabolomic profile of different Amphimedon fractions was assessed using liquid chroma-tography coupled with high-resolution mass spectrometry. Fourteen known compounds were isolated and their HCV helicase and protease activities assessed using in silico modeling of their interaction with both HCV protease and helicase enzymes to reveal their anti-HCV mechanism of action. In vitro anti-HCVactivity against HCV NS3 helicase and protease was then conducted to validate the computation results and compared to that of the SNPs. Results: Transmission electron–microscopy analysis of NPs prepared from Amphimedon total extract and petroleum ether revealed particle sizes of 8.22–14.30 nm and 8.22–9.97 nm, and absorption bands at λmax of 450 and 415 nm, respectively. Metabolomic profiling revealed the richness of Amphimedon spp. with different phytochemical classes. Bioassay-guided isolation resulted in the isolation of 14 known compounds with anti-HCV activity, initially revealed by docking studies. In vitro anti–HCV NS3 helicase and protease assays of both isolated compounds and NPs further confirmed the computational results. Conclusion: Our findings indicate that Amphimedon, total extract, petroleum ether fraction, and derived NPs are promising biosources for providing anti-HCV drug candidates, with nakinadine B and 3,4-dihydro-6-hydroxymanzamine A the most potent anti-HCV agents, possessing good oral bioavailability and penetration power.

Objective The aim of this concise review is to summarize the use of silver nanomaterials for caries prevention. Methods Two researchers independently performed a literature search of publications in English using Embase, Medline, PubMed, and Scopus databases. The keywords used were (silver nanoparticles OR AgNPs OR nano silver OR nano-silver ) AND (caries OR tooth decay OR remineralisation OR remineralization). They screened the title and abstract to identify potentially eligible publications. They then retrieved the full texts of the identified publications to select original research reporting silver nanomaterials for caries prevention. Results The search identified 376 publications, and 66 articles were included in this study. The silver nanomaterials studied were categorized as resin with silver nanoparticles (n=31), silver nanoparticles (n=21), glass ionomer cement with silver nanoparticles (n=7), and nano silver fluoride (n=7). Most (59/66, 89%) studies investigated the antibacterial properties, and they all found that silver nanomaterials inhibited the adhesion and growth of cariogenic bacteria, mainly Streptococcus mutans. Although silver nanomaterials were used as anti-caries agents, only 11 (11/66, 17%) studies reported the effects of nanomaterials on the mineral content of teeth. Eight of them are laboratory studies, and they found that silver nanomaterials prevented the demineralization of enamel and dentin under an acid or cariogenic biofilm challenge. The remaining three are clinical trials that reported that silver nanomaterials prevented and arrested caries in children. Conclusion Silver nanoparticles have been used alone or with resin, glass ionomer, or fluoride for caries prevention. Silver nanomaterials inhibit the adhesion and growth of cariogenic bacteria. They also impede the demineralization of enamel and dentin.

Objectives The first objective of this study was to prepare sodium fluoride (NaF) solution with various concentrations of polyethylene glycol-coated silver nanoparticles (PEG-AgNPs). The second objective was to study the antibacterial activity against Streptococcus mutans and the tooth-staining effect of the solution. Methods PEG-AgNPs were prepared via the one-step chemical reduction of silver acetate with thiolated polyethylene glycol. The PEG-AgNPs were characterized with ultraviolet-visible spectrometry and transmission electron microscopy. The half maximal inhibitory concentration (IC50) for the PEG-AgNPs against Streptococcus mutans and human gingival fibroblasts (HGF-1) were determined. The staining effect on dentin and enamel for the 2.5% NaF solutions with PEG-AgNPs at 12,800, 6400, 1600, and 400 ppm was investigated using digital spectrophotometry. The IC50 of the fluoridated silver nanoparticles against Streptococcus mutans were measured. Results The PEG-AgNPs have an average diameter of 2.56±0.43 nm and showed excellent stability at high ionic strength (2.5% NaF) for 18 months. The IC50 of PEG-AgNPs against Streptococcus mutans was found to be 21.16±1.08 ppm silver, which was half of IC50 against HGF-1 cells (42.36±1.12 ppm), providing a working range to kill bacteria with no harm to human cells. The formulations with different concentrations of PEG-AgNPs showed no significant staining of teeth. Combining PEG-AgNPs with NaF significantly expanded the therapeutic window against Streptococcus mutans by reducing its IC50. Conclusion A biocompatible solution of NaF with PEG-AgNPs was developed. Because it has antibacterial activity against Streptococcus mutans and no tooth-staining effect, it can be used as an anti-caries agent.

Bilal Javed,1,2 Zia-ur-Rehman Mashwani2 1Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA; 2Department of Botany, PMAS Arid Agriculture University, Rawalpindi, Punjab 46300, PakistanCorrespondence: Bilal Javed; Zia-ur-Rehman MashwaniDepartment of Botany, PMAS Arid Agriculture University, Rawalpindi, Punjab 46300, PakistanEmail javedbilal87@gmail.com; zia.botany@gmail.comBackground: Physicochemical parameters such as temperature, pH, the concentration of the AgNO3 and ratio of reactants act synergistically to influence the reaction kinetics, molecular mechanics, enzymatic catalysis and protein conformations that aid to affect the size, shape and biochemical corona of nanoparticles. The present study was performed to investigate the influence of reaction parameters on the bio-fabrication of silver nanoparticles (AgNPs) by using Mentha arvensis and to determine their potential to control the proliferation of colon cancer cells’.Methods: Plant-mediated method was used for the bio-fabrication and stabilization of AgNPs. Reaction parameters were arranged, and surface plasmon resonance (SPR) bands of AgNPs were collected by using a UV-Visible spectrophotometer. NPs were characterized structurally and optically by using SEM, AFM, EDX and DLS techniques. AgNPs and plant aqueous extract were tested against HCT116 colon cancer cells by using SRB assay, Annexin V assay and cell cycle analysis.Results: Spectrophotometric comparison of various reaction conditions manifested that 5 mM of AgNO3, 60 °C in an acidic pH and a mixing ratio of 1:9 of plant extract and AgNO3, respectively, are the optimized conditions for AgNP synthesis. Structural evaluation by SEM, AFM and particle size analysis confirmed that the NPs are < 100 nm and are anisotropic, spherical, triangular and moderately dispersed in the colloidal mixture. SRB assay expressed biomass-stabilized AgNPs as effective cytotoxic particles against HCT116 colon cancer cells, and the IC50 was measured at 1.7 μg/mL. Annexin V apoptosis assay further confirmed that the AgNPs induce apoptosis in a dose-dependent manner. Experimental evidence manifested that the AgNPs arrest cell cycle and expressed entrapment of a greater number of cells in the Sub-G1 phase, further verifying the anticancer abilities of AgNPs.Conclusion: These findings explain the synergistic effects of physicochemical parameters to optimize the phytosynthesis of biocompatible AgNPs to overcome the limitations of conventional chemotherapeutic treatments of colon cancer cells.Keywords: anticancer, cell cycle analysis, colorectal cancer, green synthesis, Mentha arvensis, reaction dynamics

Introduction Increasing bacteria resistance to antibiotics is a major problem of healthcare system. There is a need for solutions that broaden the spectrum of bactericidal agents improving the efficacy of commonly used antibiotics. One of the promising directions of search are silver nanoparticles (obtained by different methods and displaying diversified physical and chemical properties), and their combination with antibiotics. Purpose In this study, we tested the role of reactive oxygen species in the mechanism of synergistic antibacterial activity of gentamicin and Tween-stabilized silver nanoparticles against gentamicin-resistant clinical strains of Staphylococcus epidermidis. Methods Synergistic bactericidal activity of gentamicin and silver nanoparticles stabilized with non-ionic detergent (Tween 80) was tested by the checkerboard titration method on microtiter plates. Detection of reactive oxygen species was based on the chemiluminescence of luminol. Results Hydrophilic non-ionic surface functionalization of silver nanoparticles enabled the existence of non-aggregated active nanoparticles in a complex bacterial culture medium. Tween-stabilized silver nanoparticles in combination with gentamicin exhibited bactericidal activity against multidrug-resistant biofilm forming clinical strains of Staphylococcus epidermidis. A synergistic effect significantly decreased the minimal inhibitory concentration of gentamicin (the antibiotic with numerous undesirable effects). Gentamicin significantly enhanced the generation of reactive oxygen species by silver nanoparticles. Conclusion Generation of reactive oxygen species by Tween-coated metallic silver nanoparticles was significantly enhanced by gentamicin, confirming the hypothesis of oxidative-associated mechanism of the synergistic antibacterial effect of the gentamicin-silver nanoparticles complex.

Nanotechnology has recently emerged as a rapidly growing field with numerous biomedical science applications. At the same time, silver has been adopted as an antimicrobial material and disinfectant that is relatively free of adverse effects. Silver nanoparticles possess a broad spectrum of antibacterial, antifungal and antiviral properties. Silver nanoparticles have the ability to penetrate bacterial cell walls, changing the structure of cell membranes and even resulting in cell death. Their efficacy is due not only to their nanoscale size but also to their large ratio of surface area to volume. They can increase the permeability of cell membranes, produce reactive oxygen species, and interrupt replication of deoxyribonucleic acid by releasing silver ions. Researchers have studied silver nanoparticles as antimicrobial agents in dentistry. For instance, silver nanoparticles can be incorporated into acrylic resins for fabrication of removable dentures in prosthetic treatment, composite resin in restorative treatment, irrigating solution and obturation material in endodontic treatment, adhesive materials in orthodontic treatment, membrane for guided tissue regeneration in periodontal treatment, and titanium coating in dental implant treatment. Although not all authorities have acknowledged the safety of silver nanoparticles, no systemic toxicity of ingested silver nanoparticles has been reported. A broad concern is their potential hazard if they are released into the environment. However, the interaction of nanoparticles with toxic materials and organic compounds can either increase or reduce their toxicity. This paper provides an overview of the antibacterial use of silver nanoparticles in dentistry, highlighting their antibacterial mechanism, potential applications and safety in clinical treatment.