Understanding the effects of nanoparticles (NP) on immune cell functions is essential in designing safe and effective NP-based in vivo drug delivery systems. The immunomodulatory potential of gold nanoparticles (GNP) and silver nanoparticles (SNP) was investigated in vitro using murine splenic and human peripheral blood lymphocytes (PBL) in terms of effects on viability and mitogen-induced proliferation. Hydrodynamic size and number of NP were characterized using NP tracking analysis (NTA); modal diameters of GNP and SNP were 28 (±1.5) and 66 (± 2.7) nm, respectively, with a unimodal distribution. Lymphocytes were incubated with GNP or SNP in the presence/absence of B-or T-cell mitogens and proliferative responses then determined using [3 H]-thymidine incorporation. Concanavalin A (T-cell-specific) and lipopolysaccharide-(B-cell-specific) stimulated responses of murine splenic lymphocytes, as well as phytohemagglutinin (T-cell-specific) and pokeweed mitogen-(B-and T-cell specific) induced responses of human lymphocytes, were significantly inhibited by GNP (25-200 lg/ml) and SNP (12.5-50 lg/ml). However, [3 H]-thymidine incorporation by unstimulated lymphocytes was unaffected in the presence of GNP or SNP. Viability of lymphocytes was determined using trypan blue dye exclusion and was significantly inhibited only at 200 lg GNP/ml and 25 or 50 lg SNP/ml. As mitogen responses are most useful to provide supportive mechanistic information on primary immunotoxicologic functional observations, and so far more comprehensive data (in vivo and in vitro) is still needed, the results nevertheless suggest to us that GNP and SNP might potentially be able to modulate immune responses by impacting on lymphocyte activation.
ARTICLE HISTORY
Therapeutic potential and toxic effects of in vivo administered gold nanoparticles (GNPs) and silver nanoparticles (SNP) depend on distribution in tissues. Rhodamine (Rho) labeled bovine serum albumin (BSA) and chitosan (Chi) were prepared by covalent conjugation and were characterized by fluorescence spectral analysis. GNP and SNP were coated with the labeled conjugates of BSA and chitosan by adsorption. The soluble Rho‐BSA or Rho‐Chi conjugates, uncoated, and conjugate‐coated GNP, and SNP were orally administered into 8‐week‐old rats. After 24 h, rats were euthanized and the liver, kidney, spleen, and thymus were dissected. The tissues were examined ex vivo using a small animal in vivo imaging system. The liver, kidney, and thymus displayed higher fluorescence due to increased accumulation of Rho‐BSA or Rho‐Chi conjugate‐coated nanoparticles (NPs) in the tissues as compared to the spleen where lower fluorescence was noticed. Tissues obtained from rats that were administered Rho‐BSA or Rho‐Chi conjugate‐coated GNP and SNP showed tenfold higher fluorescence intensity as compared to tissues from rats that were given soluble conjugates or NP alone. The results strongly suggest significant tissue distribution of NP following oral administration.
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