title: 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.
authors.affiliation: Biomedical MRI Unit, KU Leuven, Department of Imaging and Pathology, Herestraat 49, B3000, Leuven, Belgium.
authors.forename: Bella B
authors.initials: BB
authors.lastname: Manshian
authors.affiliation: Organ Systems, Department of Development and Regeneration, KU Leuven, Herestraat 49, B3000, Leuven, Belgium.
authors.forename: Julio
authors.initials: J
authors.lastname: Jimenez
authors.affiliation: Biomedical MRI Unit, KU Leuven, Department of Imaging and Pathology, Herestraat 49, B3000, Leuven, Belgium.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.affiliation: Biomedical MRI Unit, KU Leuven, Department of Imaging and Pathology, Herestraat 49, B3000, Leuven, Belgium.
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Soenen
mesh_terms: D000072283:A549 Cells; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D012834:Silver / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D012834:Silver
keywords: cancer therapy; immunotherapy; nanomedicine; nanoparticles