title: In Vitro Administration of Gold Nanoparticles Functionalized with MUC-1 Protein Fragment Generates Anticancer Vaccine Response via Macrophage Activation and Polarization Mechanism.
abstract: Therapeutic cancer vaccines (or active immunotherapy) aim to guide the patient's personal immune system to eradicate cancer cells. An exciting approach to cancer vaccines has been offered by nanoscale drug delivery systems containing tumor associated antigens (TAAs). Their capacity to stimulate the immune system has been suggested during late years. However, the role of the macrophages as key-elements in antigen-presentation process following TAAs-containing nanosystems is not completely understood. We aimed to evaluate the effect of gold nanoparticles functionalized with mucin-1 peptide (MUC-1) on murine peritoneal macrophages. Gold nanoparticles, obtained using a modified Turkevich method, were functionalized with MUC-1 protein using Clealand's reagent. The obtained GNP-MUC-1 solution was used to treat at various concentrations monolayers of peritoneum-derived macrophages that were further analyzed using confocal and hyperspectral microscopy, ELISA assays and spectroscopic techniques. The GNP-MUC-1 nano-construct had proven to function as a powerful macrophage activator with consequent release of cytokines such as: TNF-ɑ, IL-6, IL-10 and IL-12 on peritoneal macrophages we have isolated from mice. Our results demonstrate optimization of antigen-presenting process and predominant M1 polarization following exposure GNP-MUC-1. To our best knowledge this is the first study to evaluate the anticancer effects of a newly designed nano-biocompound on the complex antigen- processing apparatus of peritoneal macrophages.
authors.affiliation: 2. Department of Nanomedicine, Institute of Gastroenterology and Hepatology, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania. ; 3. Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, no. 1 Clinicilor Street., 400006 Cluj-Napoca, Romania.
authors.forename: Teodora
authors.initials: T
authors.lastname: Mocan
authors.affiliation: 1. 3rd Surgery Clinic, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania. ; 2. Department of Nanomedicine, Institute of Gastroenterology and Hepatology, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Matea
authors.affiliation: 2. Department of Nanomedicine, Institute of Gastroenterology and Hepatology, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania. ; 4. Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; Calea Mănăștur 3-5, Cluj-Napoca 400372.
authors.forename: Flaviu
authors.initials: F
authors.lastname: Tabaran
authors.affiliation: 1. 3rd Surgery Clinic, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania. ; 2. Department of Nanomedicine, Institute of Gastroenterology and Hepatology, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania.
authors.forename: Cornel
authors.initials: C
authors.lastname: Iancu
authors.affiliation: 3. Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, no. 1 Clinicilor Street., 400006 Cluj-Napoca, Romania.
authors.forename: Remus
authors.initials: R
authors.lastname: Orasan
authors.affiliation: 1. 3rd Surgery Clinic, "Iuliu Hatieganu" University of Medicine and Pharmacy, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania. ; 2. Department of Nanomedicine, Institute of Gastroenterology and Hepatology, 19-21 Croitorilor St., 400162 Cluj-Napoca, Romania.
authors.forename: Lucian
authors.initials: L
authors.lastname: Mocan
keywords: cancer vaccine; macrophages; monoclonal antibodies; peptides