Nanosilver: An Old Antibacterial Agent with Great Promise in the Fight against Antibiotic Resistance.

Antibiotic resistance in bacteria is a major problem worldwide that costs 55 billion USD annually for extended hospitalization, resource utilization, and additional treatment expenditures in the United States. This review examines the roles and forms of silver (e.g., bulk Ag, silver salts (AgNO3), and colloidal Ag) from antiquity to the present, and its eventual incorporation as silver nanoparticles (AgNPs) in numerous antibacterial consumer products and biomedical applications. The AgNP fabrication methods, physicochemical properties, and antibacterial mechanisms in Gram-positive and Gram-negative bacterial models are covered. The emphasis is on the problematic ESKAPE pathogens and the antibiotic-resistant pathogens of the greatest human health concern according to the World Health Organization. This review delineates the differences between each bacterial model, the role of the physicochemical properties of AgNPs in the interaction with pathogens, and the subsequent damage of AgNPs and Ag+ released by AgNPs on structural cellular components. In closing, the processes of antibiotic resistance attainment and how novel AgNP-antibiotic conjugates may synergistically reduce the growth of antibiotic-resistant pathogens are presented in light of promising examples, where antibiotic efficacy alone is decreased.

Experimental and Theoretical Screening of Core Gold Nanoparticles and Their Binding Mechanism to an Anticancer Drug, 2-Thiouracil.

This study demonstrated the capability of two readily available optical spectroscopy tools, namely UV-Vis absorption spectrophotometry and Raman/surface-enhanced Raman spectroscopy, to select in a rapid and noninvasive manner the most homogenous gold nanoparticle (AuNP) models and to identify their chemical binding mechanism to 2-thiouracil (2-TU). 2-TU is an anticancer drug of great promise in the antiproliferative and photothermal therapies of cancer. The citrate-capped AuNPs emerged as the most stable as well as time- and cost-effective AuNP model out of the three widely used colloidal nanocores (citrate-, borohydride-citrate-, and sodium dodecyl sulfate (SDS)-capped AuNPs) that were examined. 2-TU chemically attached to the relatively monodispersed AuNPs via a chemisorption mechanism. The 2-TU-AuNPs complex formed through the covalent bonding of the S atom of 2-TU to the nanosurface in a vertical orientation. The spectroscopic results were then confirmed with the help of density functional theory (DFT) calculations and other physicochemical characterization tools for nanomaterials such as transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential. Overall, the purified 2-TU-AuNPs were found to be spherical, had an average diameter of 25 ± 2 nm, a narrow size distribution (1-30 nm), a sharp localized surface plasmon resonance (LSPR) peak at 525 nm, and a negative surface charge (-14 mV).

Biodistribution and toxicity of antimicrobial ionic silver (Ag+) and silver nanoparticle (AgNP+) species after oral exposure, in Sprague-Dawley rats.

Although antimicrobial nanosilver finds numerous applications in the health and food industries, the in vivo toxicity of positively charged silver nanoparticles (AgNPs+) and relevant controls are largely unexplored. This study investigates the relationship between the biodistribution and toxicity of the well-known cetyltrimethylammonium bromide (CTAB)-capped AgNPs+ in 6-weeks old female Sprague-Dawley rats, at sublethal doses. Amounts comparative to those leaked from food products or considered for animal feed were administered through daily water intake, for an 18-day period: AgNPs+ (40 µg mL-1), Ag+ (40 µg mL-1), antimicrobial CTAB+ (24 µg mL-1) and tap water. All exposures except for the water control had adverse effects on the health and systemic functions of rats (e.g., lethargy, hepatomegaly, splenomegaly, impediment of bone development, and/or heightened immune response). Although the total Ag accumulation in tissues (1.4-1.6 µg of Ag/g of liver, spleen, jejunum, and brain) was comparable for the two Ag species, AgNPs+ were generally more toxic than Ag+, particularly in spleen (0.8 µg Ag/g). Significantly reduced euthanasia time, alopecia, inflammatory responses in spleen, fragile veins, and enhanced lymphocytosis were observed only for AgNPs+. Overall, this study raises health concerns about the ingestion of capped-AgNPs+ or Ag+ by first-hand consumers and industry workers.

Silver Nanocolloids Loaded with Betulinic Acid with Enhanced Antitumor Potential: Physicochemical Characterization and In Vitro Evaluation.

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models-hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

SERS-based differential diagnosis between multiple solid malignancies: breast, colorectal, lung, ovarian and oral cancer.

PURPOSE: Surface-enhanced Raman scattering (SERS) spectroscopy on serum and other biofluids for cancer diagnosis represents an emerging field, which has shown promising preliminary results in several types of malignancies. The purpose of this study was to demonstrate that SERS spectroscopy on serum can be employed for the differential diagnosis between five of the leading malignancies, ie, breast, colorectal, lung, ovarian and oral cancer. PATIENTS AND METHODS: Serum samples were acquired from healthy volunteers (n=39) and from patients diagnosed with breast (n=42), colorectal (n=109), lung (n=33), oral (n=17), and ovarian cancer (n=13), comprising n=253 samples in total. SERS spectra were acquired using a 532 nm laser line as excitation source, while the SERS substrates were represented by Ag nanoparticles synthesized by reduction with hydroxylamine. The classification accuracy yielded by SERS was assessed by principal component analysis-linear discriminant analysis (PCA-LDA). RESULTS: The sensitivity and specificity in discriminating between cancer patients and controls was 98% and 91%, respectively. Cancer samples were correctly assigned to their corresponding cancer types with an accuracy of 88% for oral cancer, 86% for colorectal cancer, 80% for ovarian cancer, 76% for breast cancer and 59% for lung cancer. CONCLUSION: SERS on serum represents a promising strategy of diagnosing cancer which can discriminate between cancer patients and controls, as well as between cancer types such as breast, colorectal, lung ovarian and oral cancer.

Combining SERS analysis of serum with PSA levels for improving the detection of prostate cancer.

AIM: Previous studies regarding surface-enhanced Raman scattering (SERS) of serum have shown promising initial results in discriminating prostate cancer, a strategy which could complement standard tests such as the prostate-specific antigen (PSA). MATERIALS & METHODS: SERS spectra of serum samples were combined with serum PSA levels to improve the discrimination accuracy between prostate cancer and nonmalignant pathologies in a cohort of 54 patients using principal component analysis-linear discriminant analysis (PCA-LDA). RESULTS & DISCUSSION: Combining SERS spectra with serum PSA levels in a single PCA-LDA model could discriminate between the two groups with an overall accuracy of 94%, yielding better results than either method alone. CONCLUSION: These results highlight that combining SERS-based cancer screening with serum PSA levels represents a promising strategy for improving the accuracy of prostate cancer diagnosis.

Size selection and concentration of silver nanoparticles by tangential flow ultrafiltration for SERS-based biosensors.

A proposed tangential flow ultrafiltration method was compared to the widely used ultracentrifugation method for efficiency and efficacy in concentrating, size selecting, and minimizing the aggregation state of a silver nanoparticle (AgNP) colloid while probing the AgNPs' SERS-based sensing capabilities. The ultrafiltration method proved to be more efficient and more effective and was found to tremendously boost the SERS-based sensing capabilities of these AgNPs through the increased number of homogeneous SERS hot spots available for a biotarget molecule within a minimal focal volume. Future research studies and applications addressing the physiochemical properties or biological impact of AgNPs would greatly benefit from ultrafiltration for its ability to generate monodisperse colloidal nanoparticles, to eliminate excess toxic chemicals from nanoparticle synthesis, and to obtain minimum levels of aggregation during nanoparticle concentration.