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Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

ABSTRACT: The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

SUBMITTER: Orlowski P

PROVIDER: S-EPMC4130517 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

Orlowski Piotr P Tomaszewska Emilia E Gniadek Marianna M Baska Piotr P Nowakowska Julita J Sokolowska Justyna J Nowak Zuzanna Z Donten Mikolaj M Celichowski Grzegorz G Grobelny Jaroslaw J Krzyzowska Malgorzata M

PloS one 20140812 8

The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus ...[more]

PMID: 25117537

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Project description:Silver nanoparticles (AgNPs) are promising new antimicrobial agents against a wide range of skin and mucosal pathogens. However, their interaction with the immune system is currently not fully understood. Dendritic cells (DCs) are crucial during development of T cell-specific responses against bacterial and viral pathogens. We have previously shown that tannic acid-modified silver nanoparticles (TA-AgNPs) consist of a promising microbicide against HSV-2. The aim of this study was to compare the ability of TA-AgNPs or TA-AuNPs of similar sizes (TA-Ag/AuNPs) to induce DCs maturation and activation in the presence of HSV-2 antigens when used at non-toxic doses. First, we used JAWS II DC line to test toxicity, ultrastructure as well as activation markers (MHC I and II, CD40, CD80, CD86, PD-L1) and cytokine production in the presence of TA-Ag/AuNPs. Preparations of HSV-2 treated with nanoparticles (TA-Ag/AuNPs-HSV-2) were further used to investigate HSV-2 antigen uptake, activation markers, TLR9 expression, and cytokine production. Additionally, we accessed proliferation and activation of HSV-2-specific T cells by DCs treated with TA-AgNP/AuNPs-HSV-2. We found that both TA-AgNPs and TA-AuNPs were efficiently internalized by DCs and induced activated ultrastructure. Although TA-AgNPs were more toxic than TA-AuNPs in corresponding sizes, they were also more potent stimulators of DCs maturation and TLR9 expression. TA-Ag/AuNPs-HSV-2 helped to overcome inhibition of DCs maturation by live or inactivated virus through up-regulation of MHC II and CD86 and down-regulation of CD80 expression. Down-regulation of CD40 expression in HSV-2-infected DCs was reversed when HSV-2 was treated with TA-NPs sized >30?nm. On the other hand, small-sized TA-AgNPs helped to better internalize HSV-2 antigens. HSV-2 treated with both types of NPs stimulated activation of JAWS II and memory CD8+?T cells, while TA-AgNPs treatment induced IFN-? producing CD4+?and CD8+?T cells. Our study shows that TA-AgNPs or TA-AuNPs are good activators of DCs, albeit their final effect upon maturation and activation may be metal and size dependent. We conclude that TA-Ag/AuNPs consist of a novel class of nano-adjuvants, which can help to overcome virus-induced suppression of DCs activation.

Project description:Abstract Background Most traditional wound dressings only partially meet the needs of wound healing because of their single function. Patients usually suffer from the increasing cost of treatment and pain resulting from the frequent changing of wound dressings. Herein, we have developed a mutifunctional cryogel to promote bacterial infected wound healing based on a biocompatible polysaccharide. Methods The multifunctional cryogel is made up of a compositive scaffold of chitosan (CS), gelatin (Gel) and tannic acid (TA) and in situ formed silver nanoparticles (Ag NPs). A liver bleeding rat model was used to evaluate the dynamic hemostasis performance of the various cryogels. In order to evaluate the antibacterial properties of the prepared cryogels, gram-positive bacterium Staphylococcus aureus (S. aureus) and gram-negative bacterium Escherichia coli (E. coli) were cultured with the cryogels for 12 h. Meanwhile, S. aureus was introduced to cause bacterial infection in vivo. After treatment for 2 days, the exudates from wound sites were dipped for bacterial colony culture. Subsequently, the anti-inflammatory effect of the various cryogels was evaluated by western blotting and enzyme-linked immunosorbent assay. Finally, full-thickness skin defect models on the back of SD rats were established to assess the wound healing performances of the cryogels. Results Due to its porous structure, the multifunctional cryogel showed fast liver hemostasis. The introduced Ag NPs endowed the cryogel with an antibacterial efficiency of >99.9% against both S. aureus and E. coli. Benefited from the polyphenol groups of TA, the cryogel could inhibit nuclear factor-κB nuclear translocation and down-regulate inflammatory cytokines for an anti-inflammatory effect. Meanwhile, excessive reactive oxygen species could also be scavenged effectively. Despite the presence of Ag NPs, the cryogel did not show cytotoxicity and hemolysis. Moreover, in vivo experiments demonstrated that the biocompatible cryogel displayed effective bacterial disinfection and accelerated wound healing. Conclusions The multifunctional cryogel, with fast hemostasis, antibacterial and anti-inflammation properties and the ability to promote cell proliferation could be widely applied as a wound dressing for bacterial infected wound healing. Graphical Abstract Graphical Abstract

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Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

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Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

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