Alteration in Inflammasome Cytokine Profile and Functional Plasticity of Macrophage Phenotype in Arsenic(0) Nanoparticle Treated Murine Fibrosarcoma

• Published in: BioNanoScience 2022-06, Vol.12 (2), p.380-392
• Main Authors: Das, Biswajit, Pal, Anjali, Pal, Ramkrishna, Kumar, Rajeev, Das, Rakesh, Dey, Debjani, Devi, Juri, Sengupta, Mahuya
• Format: Article
• Language: English
• Subjects: 3-Methylcholanthrene; Acetic acid; Arsenic; Biological and Medical Physics; Biomaterials; Biophysics; Circuits and Systems; Cytokines; Engineering; Fibrosarcoma; Functional plasticity; Genotype & phenotype; IL-1β; Immunology; In vivo methods and tests; Inflammasomes; Inflammation; Macrophages; Monocytes; Nanoparticles; Nanotechnology; Phenotypes; Phenotypic plasticity; Phorbol 12-myristate 13-acetate; Population; Surveillance; Tumor microenvironment; Tumor necrosis factor-α; Tumors
• ISSN: 2191-1630; 2191-1649
• DOI: 10.1007/s12668-021-00936-0

Macrophages are the decisive cells of immunological surveillance, and can adopt a variety of phenotypes based on the stimuli they receive; two of the best-characterized are pro-inflammatory “M1” phenotype and anti-inflammatory “M2” phenotype. Circulating monocytes are recruited into a tumor microenvironment, where they mature into tumor-associated macrophages (TAMs). TAMs population is constituted primarily by M2 and a small fraction of M1 phenotypes which guide tumorigenic cells to escape from immunological surveillance. The present study is focused on the characterization of TAMs population in chemically induced murine fibrosarcoma inducted with a single subcutaneous dose of 3-methylcholanthrene (0.5 mg/mice) and repeated dose of phorbol 12-myristate 13-acetate (10 µg/mice). Arsenic nanoparticles (AsNPs), having proved their potential for tumor regression, were investigated for modulation of TAMs phenotype in the tumor microenvironment. The in vivo study elaborates an alteration in the TAM population with an increase in the “M1-like” phenotype in the tumor microenvironment after treatment with AsNPs. At the end of the treatment regime, the difference between the mean ± SEM of serum level (pg/ml) of IL-1β and TNF-α among untreated and AsNP-treated tumor-bearing mice were 2.731 ± 0.8056 and 256.0 ± 33.41, respectively. In vitro study also confirmed an increase in proinflammatory cytokine released by macrophages after AsNP treatment. The difference between means ± SEM of TNF-α released (pg/ml) by untreated TAMs and TAMs treated with 1 µM AsNP was 120 ± 7.90. Thus treatment with AsNPs may enrich the “M1-type TAMs” population through the interaction of inflammasome-associated cytokines and ROS. The observation may encourage workers to investigate the chemo-immunotherapeutic potential of arsenic nanoparticles to re-educate TAMs. Graphical abstract