An interferon-γ-delivery system based on chitosan/poly(γ-glutamic acid) polyelectrolyte complexes modulates macrophage-derived stimulation of cancer cell invasion in vitro.

Abstract:

:Macrophages represent a large component of the tumour microenvironment and are described to establish interactions with cancer cells, playing crucial roles in several stages of cancer progression. The functional plasticity of macrophages upon stimulation from the environment makes them susceptible to the influence of cancer cells and also renders them as promising therapeutic targets. In this work, we describe a drug delivery system to modulate the phenotype of macrophages, converting them from the pro-tumour M2 phenotype to the anti-tumour M1 phenotype, based on the incorporation of a pro-inflammatory cytokine (interferon-γ) in chitosan (Ch)/poly(γ-glutamic acid) (γ-PGA) complexes. Ch is a biocompatible cationic polysaccharide extensively studied and γ-PGA is a biodegradable, hydrophilic and negatively charged poly-amino acid. These components interact electrostatically, due to opposite charges, resulting in self-assembled structures that can be designed to deliver active molecules such as drugs and proteins. Ch and γ-PGA were self-assembled into polyelectrolyte multilayer films (PEMs) of 371nm thickness, using the layer-by-layer method. Interferon-γ (IFN-γ) was incorporated within the Ch layers at 100 and 500ng/mL. Ch/γ-PGA PEMs with IFN-γ were able to modulate the phenotype of IL-10-treated macrophages at the cell cytoskeleton and cytokine profile levels, inducing an increase of IL-6 and a decrease of IL-10 production. More interestingly, the pro-invasive role of IL-10-treated macrophages was hindered, as their stimulation of gastric cancer cell invasion in vitro decreased from 4 to 2-fold, upon modulation by Ch/γ-PGA PEMs with IFN-γ. This is the first report proposing Ch/γ-PGA PEMs as a suitable strategy to incorporate and release bioactive IFN-γ with the aim of modulating macrophage phenotype, counteracting their stimulating role on gastric cancer cell invasion.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Cardoso AP,Gonçalves RM,Antunes JC,Pinto ML,Pinto AT,Castro F,Monteiro C,Barbosa MA,Oliveira MJ

doi

10.1016/j.actbio.2015.05.022

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

157-171

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(15)00246-9

journal_volume

23

pub_type

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