In Vitro Administration of Gold Nanoparticles Functionalized with MUC-1 Protein Fragment 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.

What is new in the histogenesis of granulomatous skin diseases?

“…In terms of macrophage polarization, M2 macrophages were observed in granulomatous infiltration surrounding necrobiotic collagens . The degenerated collagen may trigger M2 polarization of macrophages to promote tissue remodeling.…”

“…In addition to the immune reaction, extracellular matrix remodeling is a key feature of granuloma annulare. Torocsik et al 54 demonstrated that infiltrating macrophages showed M2 macrophages that were alternatively activated by Factor XIII-A + . M2 macrophages are typically induced by Th2-dominated responses, such as IL-4 stimulation.…”

“…In terms of macrophage polarization, M2 macrophages were observed in granulomatous infiltration surrounding necrobiotic collagens. 54 The degenerated collagen may trigger M2 polarization of macrophages to promote tissue remodeling. However, similar to GA, whether collagen degradation occurs first and is followed by macrophage infiltration for extracellular remodeling, or whether the inflammatory reaction directly induces collagen degeneration, is under discussion.…”

Advances and Opportunities in Nanoparticle‐ and Nanomaterial‐Based Vaccines against Bacterial Infections

“…The adjuvanticity of the gold nanoparticle is best illustrated in experiments that treat macrophages and BMDCs with gold nanoparticles. Following coincubation, these professional antigen‐presenting cells not only exhibited an activated phenotype, but also produced significant levels of proinflammatory cytokines, including TNF‐α, IL‐6, and IL‐12 . These cytokines provide essential immunopotentiating signals that trigger humoral and cellular immunities.…”

Laser thermal ablation of multidrug-resistant bacteria using functionalized gold nanoparticles

“…[15][16][17][18][19][20][21][22] Various types of GNP complexes (protein-coated GNPs, peptide-coated GNPs, GNPs coated with nucleic acids, drugs) are available for delivery to cells and organs.…”