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Theranostics 2020, Vol. 10, Issue 20 capped AgNPs exhibited stronger inhibition to Gram-negative organisms, which were primarily responsible for periodontal infection [295]. Vaccine Adjuvant Vaccination is one of the most effective methods to prevent infectious diseases and manage healthcare costs [296]. Traditional vaccines have good immunogenicity due to the complex nature of the formulation and the presence of adjuvants. However, purified preparations lack immunogenicity, which makes the addition of adjuvants essential. Adjuvants can simultaneously reduce the amount of antigen required, shorten the time needed for a protective threshold of antibody production and improve the intensity of the elicited responses, stimulate long-term memory responses to reduce the requirement of repeated vaccinations. Yingying Xu et al. [297] firstly reported the remarkable immunological adjuvant effect of AgNPs both in vitro and in vivo using model antigens ovalbumin and bovine serum albumin in 2013. After intraperitoneal or subcutaneous immunization of mice, AgNPs increased the production of serum antigen-specific IgG, as well as antigen-specific IgE, indicating that AgNPs stimulated Th2-biased immune responses. Further study of the mechanism of adjuvant revealed that AgNPs could recruit and activate local leukocytes and macrophages. Vahid Asgary et al. [298] evaluated AgNPs as an adjuvant for the rabies vaccine in 2014 and 2016, respectively. They found that although the load of AgNPs could significantly increase the immune responses by arising neutralizing antibody against rabies virus in mice, the lowest concentration of virus-loaded AgNPs decreased cell viability. This limitedtheuseofAgNPsasanadjuvantinrabies virus. They then challenged the green synthesis of AgNPs using leaf extract of Eucalyptus procera and added AgNPs as an adjuvant in rabies veterinary vaccine, following by estimating vaccine efficacy in mice and dogs. They confirmed that the vaccine loaded with a suitable concentration of AgNPs was nontoxic [299]. Antidiabetic Agent Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia. DM is due to either insufficient insulin secretion or insulin resistance of the cell. Commonly used hypoglycemic agents can lower blood sugar by promoting secretion of insulin or increasing cell sensitivity [300]. In recent studies, it is noticed that AgNPs synthesized by plant extracts exhibit antidiabetic potential. Arumugam et al. [301] synthesized AgNPs using leaf extract of Solanum nigrum and evaluated the anti-hyperglycemic 9015 effect in alloxan-induced diabetic rats. They found that the blood glucose level of diabetic rats decreased when treated with AgNPs for 14 days and 21 days without significant acute toxicity. And they assessed glucose tolerance of AgNPs in diabetic rats. The results showed that AgNPs exhibited a good hypoglycemic effect compared to glibenclamide, a standard antidiabetic drug. Saratale et al. [4] demonstrated that AgNPs synthesized by leaf extract of Argyreia nervosa exhibited antidiabetic activity via inhibiting α-amylase and α-glucosidase. These two carbohydrate digestive enzymes contribute to decompose carbohydrates into monosaccharides. The antidiabetic mechanism of AgNPs is still unclear. Jihan Hussein et al. [302] hypothesized that AgNPs might influence insulin signaling pathway or insulin sensitivity in diabetic rats. The results supposed that AgNPs could activate protein kinase C and PI3K pathway at the insulin receptor substrate level, as well as inhibit protein kinase C isozymes, thus effectively enhance insulin secretion and sensitivity. It was highlighted that AgNPs were effective in reducing insulin resistance and DNA damage. Biosensing and Imaging Surface-enhanced Raman scattering (SERS) has attracted the attention of noble metals with Raman signals in many application strategies, including biochemical sensing, analytical chemistry, and materials science [303]. Among these nanomaterials, AgNPs can be used as a cost-effective surface- enhanced Raman scattering substrate. Nanoparticles containing AgNPs can be used as biosensors to detect blood glucose, enzymes, molecular markers of tumor cells, pathogens, etc. For example, Jiang et al. [304] prepared silver-containing nanocomposites as acetylcholinesterase biosensors for electrochemical detection of organophosphorus pesticides. AgNPs improved the electrical conductivity and biocompatibility of nanocomposites and made them more suitable for enzyme activity and stability. Anderson et al. [305] prepared a high-sensitivity nonenzymatic biosensor for the detection of glucose using AgNPs as a conductive additive. Both the porous nanostructures of AgNPs and large surface areas of carriers enhanced the interaction sites between AgNPs and electrode/glucose, which could accelerate the electron transfer of AgNPs and therefore improve the sensitivity of the biosensor. Although the electrochemical characteristics and Raman scattering make AgNPs exhibit good application prospects in the field of biosensing, the matrix composition may affect their SERS and reduce the detection sensitivity. Therefore, it is necessary to modify AgNPs in order to improve the sensitivity of http://www.thno.orgPDF Image | Silver nanoparticles Synthesis medical applications safety
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