Immunomodulatory activities of curcumin-stabilized silver nanoparticles: Efficacy as an antiretroviral therapeutic

Immunol Invest. 2017 Nov;46(8):833-846. doi: 10.1080/08820139.2017.1371908.

Abstract

We synthesized and characterized curcumin-stabilized silver nanoparticles (Cur-AgNP) and found them to be 45 nm by dynamic light scattering with a maximum absorbance at 406 nm. We evaluated Cur-AgNP for immunomodulatory activities and their potential as an antiretroviral agent. The antiretroviral effects of Cur-AgNP were determined in ACH-2 cells latently infected with human immunodeficiency virus (HIV)-1. ACH-2 cells, 200,000/ml, were treated with Cur-AgNP for 24-48 h. Expression of HIV-1 LTR and p24, the pro-inflammatory cytokines, IL-1β, TNF-α, and NF-κB was quantitated. Treatment of ACH-2 cells latently infected with HIV-1 with Cur-AgNP produced no toxic effects but significantly inhibited the expression of HIV-1 LTR (-73%, P < 0.01) and p24 (-57%, P < 0.05), IL-1βα (-61%, P < 0.01), TNF-αα (-54%, P < 0.05), IL-6 (-68%, P < 0.01), and NF-κB (-79%, P < 0.0001) as compared to untreated controls. Thus, Cur-AgNP have therapeutic potential as direct antiretroviral agents, as well as having immunomodulatory activities inhibiting the expression of pro-inflammatory mediators induced by infection with HIV-1. Experimental controls, such as curcumin alone, and conventional silver nanoparticles capped with citric acid, produced no similar biological effects. We conclude that treatment of HIV-1 infected cells with Cur-AgNP significantly reduced replication of HIV by inhibition of NF-κB nuclear translocation and the downstream expression of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. Subsequent in vivo studies with Cur-AgNP using a humanized mouse model of HIV infection are underway.

Keywords: Antiretroviral; Curcumin; HIV-1; Immunomodulation; Nano-therapeutics; Silver Nanoparticles.

MeSH terms

  • Anti-Retroviral Agents / pharmacology*
  • Cell Line
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Cytokines / metabolism
  • Gene Expression Regulation
  • HIV Core Protein p24 / metabolism
  • HIV Infections / immunology*
  • HIV Long Terminal Repeat / genetics
  • HIV-1 / physiology*
  • Humans
  • Immunologic Factors / pharmacology*
  • Inflammation Mediators / metabolism
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / therapeutic use*
  • NF-kappa B / metabolism
  • Silver / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • T-Lymphocytes / virology
  • Virus Latency
  • Virus Replication

Substances

  • Anti-Retroviral Agents
  • Cytokines
  • HIV Core Protein p24
  • Immunologic Factors
  • Inflammation Mediators
  • NF-kappa B
  • Silver
  • Curcumin