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. 2015 May 15;6(6):583-92.
doi: 10.7150/jca.11567. eCollection 2015.

In Vitro Administration of Gold Nanoparticles Functionalized with MUC-1 Protein Fragment Generates Anticancer Vaccine Response via Macrophage Activation and Polarization Mechanism

Teodora Mocan  1 , Cristian Matea  2 , Flaviu Tabaran  3 , Cornel Iancu  2 , Remus Orasan  4 , Lucian Mocan  2
Affiliations

In Vitro Administration of Gold Nanoparticles Functionalized with MUC-1 Protein Fragment Generates Anticancer Vaccine Response via Macrophage Activation and Polarization Mechanism

Teodora Mocan et al. J Cancer. .

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.

Keywords: cancer vaccine; macrophages; monoclonal antibodies; peptides.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
I. AFM images GNP-MUC-1: A. 2D image of MUC-1 functionalized GNPs; B. Cross section graph of a single gold nanoparticle functionalized with MUC-1; C. 3D image of MUC-1 functionalized GNPs; II. ATR-FT-IR spectra of GNP and GNP-MUC-1 samples (GNP sample absorption bands at 1586 cm-1 and 1395 cm-1 (red line); GNP-MUC-1 sample absorption bands at 1628 cm-1 and 1542 cm-1 (blue line).
Figure 2
Figure 2
Peritoneal macrophages following different exposures. Organelle staining (GA- green; ER-red) and nuclei staining (DAPI). (30X)
Figure 3
Figure 3
Peritoneal macrophages following different exposures. ELISA results for I-10, IL-12, Tnf-alpha amd IL-6 serum levels. Bars represent mean. Error bars represent standard error of mean.
Figure 4
Figure 4
Peritoneal macrophages following different exposures. Aggresome formation (Proteostat red staining) and nuclei staining (DAPI). (25X)
Figure 5
Figure 5
I. Viability/proliferation assay results. Cells were exposed to GNP-MUC-1 in respective concentration or cell culture media alone (control), for 6 hours, 37ᴼC, 5%CO2. Bars represent mean. Error bars represent standard error of mean. II. UV-Vis spectra of cell lysate following GNP-MUC-1 exposure (6 hrs. 50μg/mL GNP-MUC-1) III. Dark-field image at 40X magnification of peritoneal macrophages culture incubated with GNP-MUC-1 for 6 hrs. Cells have been subject to washing, fixing and immobilization before images capture with CytoViva system. Four panels: A) control group; B) cells exposed to 12.5μg/mL; C) cells exposed to 25μg/mL; D) cells exposed to 50 μg/mL. .Scale bars represent 10μM.
See this image and copyright information in PMC

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