Mushroom Carboxymethylated β-d-Glucan Functions as a Macrophage-Targeting Carrier for Iron Oxide Nanoparticles and an Inducer of Proinflammatory Macrophage Polarization for Immunotherapy.
Yuting SuFan YangLei ChenPeter Chi-Keung CheungPublished in: Journal of agricultural and food chemistry (2022)
β-d-glucans have the potential of serving as both macrophage-targeted carriers and immune stimulators via inducing trained immunity in macrophages. In this study, a carboxymethylated β-glucan from mushroom sclerotium of Pleurotus tuber-regium (CMPTR) was combined with iron oxide nanoparticles (IONPs) to form nanocomplexes (CMPTR/IONPs) with particle size around 193 ± 7 nm, which could exert a concerted effect on inducing proinflammatory M1 phenotype macrophages for immunotherapy. This nanocomplex exhibited good stability and low cytotoxicity (over 80% cellular viability of RAW 264.7 and THP-1) and higher cellular uptake by murine macrophages compared with B16F10 cells ( p < 0.05). CMPTR/IONPs could convert M2-like bone marrow-derived macrophages into M1 phenotypes with upregulated expression of pro-inflammatory cytokines (IL12 and TNF-α, p < 0.05) and reduced immune-suppressive cytokines (IL10 and TGF-β, p < 0.05). Such polarization was mediated by the combined signaling regulatory factors, including IONP-stimulated IRF5 and CMPTR-triggered TLRs-NF-κB pathways ( p < 0.05). Accordingly, CMPTR could have a dual function as a macrophage-targeting carrier for IONPs and an immunostimulant to induce inflammatory M1 macrophage polarization for immunotherapy.
Keyphrases
- iron oxide nanoparticles
- adipose tissue
- cancer therapy
- induced apoptosis
- oxidative stress
- signaling pathway
- poor prognosis
- photodynamic therapy
- transcription factor
- transforming growth factor
- drug delivery
- risk assessment
- immune response
- lps induced
- climate change
- cell death
- endoplasmic reticulum stress
- nuclear factor
- toll like receptor