Presence of an Immune System Increases Anti‐Tumor Effect of Ag Nanoparticle Treated Mice

Abstract

To date, most nanomedical studies rely on the use of immune-deficient mice in which the contribution of the immune system on the applied therapy is ignored. Here, the degradation of silver nanoparticles (Ag NPs) is exploited as a means to treat subcutaneous tumor models in mice. To investigate the impact of the immune system, the same tumor cell type (KLN 205 murine squamous cell carcinoma) is used in a xenograft model in NOD SCIDγ immune-deficient mice and as a syngeneic model in immune-competent DBA/2 mice. The Ag NPs are screened for their cytotoxicity on various cancer cell lines, indicating a concentration-dependent induction of oxidative stress, mitochondrial damage, and autophagy on all cell types tested. At subcytotoxic concentrations, prolonged cellular exposure to the Ag NPs results in toxicity due to NP degradation and the generation of toxic Ag ions. At subcytotoxic conditions, the NPs are found to cause inflammation in vitro. Similar results are obtained in the immune-competent mouse model, where clear inflammation is observed after treatment of the implanted tumors with Ag NPs. This inflammation leads to an ongoing antitumoral effect, which results in a significantly reduced tumor growth compared to Ag NP-treated tumors in an immune-deficient model.

<p>Silver Decorated Mesoporous Carbons for the Treatment of Acute and Chronic Wounds, in a Tissue Regeneration Context</p>

“…These opposite effects on inflammation, at 4 hrs and 48 hrs reflect those reported by many works (in which both activation of the inflammatory pathways [28][29][30][31] and downregulation of proinflammatory cytokines 32,33 are demonstrated in vitro and in vivo) and could be of particular interest in a wound healing context, because an immediate short-term increase of inflammation, followed by downregulation, are the main signals required for an effective wound healing process. As highly tunable materials, silver-doped mesoporous carbon materials could be tailored to achieve the desired tissue regeneration function, to be applied in a variety of pathological conditions, from acute wounds to ulcers and burn wounds.…”

A Current Overview of the Biological and Cellular Effects of Nanosilver

“…The nuclear factor kappa B (NF-κB) pathway is involved in the cellular response to various stresses including oxidative stress and is involved in the start of inflammation. Phosphorylation of I-κB kinases (IKK), in response to ROS, leads to the release of NF-κB dimers from inhibitory I-κB proteins in the cytosol, allowing them to enter the nucleus and activate gene expression leading to an inflammatory cellular response [ 91 ]. Cyclooxygenase-2 (COX-2) is a pro-inflammatory mediator during acute inflammation and is induced by cytokines such as IL-1β and TNF-α [ 90 , 92 ].…”

A Current Overview of the Molecular Effects of Nanosilver

“…The nuclear factor kappa B (NF-B) pathway is involved in the cellular response to various stresses including oxidative stress, and is involved in the start of inflammation. Phosphorylation of I-kappaB kinases (IKK) in response to ROS leads to the release of NF-B dimers from inhibitory I-B proteins, allowing them to enter the nucleus and activate gene expression leading to an inflammatory cellular response [92].…”

“…The NF-B and AP1 pathways were activated by nanosilver (10 and 75 nm, citrate and PVPcoated) in stable luciferase-reporter HepG2 cells [47] and in N27 neurons [67]. Non-toxic nanosilver (citrate-coated, 5 nm) treatment activated the NFƙB pathway in human cervical cancer cells (HeLa) and A549 cells, and an increase in the cellular immune response was seen as an increase in the pro-inflammatory cytokine IL-1α [92]. The levels of IL-6 and IL-8 increased in hMSCs treated with non-toxic nanosilver (46 nm) treatment) [54].…”