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.

Keywords: cancer therapy; immunotherapy; nanomedicine; nanoparticles.