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Dynamics of Cobalt Oxide Nanoparticles in the Activation of Reactive Oxygen Species Induced Inflammation and Immunomodulation

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Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

Abstract

The progress of nanoparticles (NPs) in cancer therapy introduces a better efficacy and lower toxicity for treatment. The cobalt oxide nanoparticles (CoO NPs) were prepared by the calcination method. The nano states of the particles were confirmed by different available physio-chemical estimations. The CoO NPs induce toxicity by leaching of Co2+ ions that strongly trigger the generation of reactive oxygen species (ROS) and activate the caspase cascade followed by necrosis on three different cancer cell lines (jurkat, KG1-A, and K562 cells) as well as the normal counterparts. The toxicity of the CoO NPs was minimized by using different surface modifying agents, such as phosphonomethyl imminodiacetic acid (PMIDA) and chitosan (CS). Surface modifications significantly reduced the Co2+ ion release into the media and reduced the toxicity of surface-modified CoO NPs to normal cells, whereas in the cancer microenvironment, modified NPs liberate Co2+ ions which induced anticancer activity by activating ROS in association with TNF-α and p38 MAPK, followed by activation of caspase cascade in both in vitro and in vivo systems. Among the two, the PMIDA-CoO NPs showed better activity at low concentrations. Independent treatment of PMIDA-CoO NPs could trigger the release of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), and decrease the production of interleukin 10 (IL-10) from lymphocytes and macrophage and produced a pro-inflammatory response.

The surface pendant –COOH group of PMIDA-CoO NPs showed an excellent binding affinity with cancer cell lysate (CL), used as an antigen. The protein antigen conjugated PMIDA-CoO NPs stimulated the macrophage and produced a strong anticancer immune response. The antitumor activity of the antigen conjugated nanoparticle (CL-PMIDA-CoO NPs) pulsed macrophages were tested on a human oral carcinoma cell line (KB) in vitro. The modified CL-PMIDA-CoO NPs upregulated IFN-γ, TNF-α, and induced an anticancer immune response by activating macrophages. The use of nuclear factor kappa beta (NF-κβ), TNF-α, and Cyclooxygenase-2 (COX-2) inhibitors confirmed the ability of the CL–PMIDA–CoO nano-complex to induce TNF-α associated immunostimulation. CL–PMIDA–CoO nanoparticles efficiently increased the CD4+ population. In vivo immunization of antigen conjugated PMIDA-CoO NPs induced an antigen-specific Immunoglobulin G (IgG) response and amplified the antibody dependent cellular cytotoxic (ADCC) effect. The cell lysate conjugated PMIDA-CoO NPs successfully activated the antigen presenting cells (APCs) as evinced by the elevated level of IFN-γ and TNF-α in serum. Additionally, the nanoconjugate can re-modulate the immune-suppressive tumor-associated macrophages towards pro-tumor macrophage by activating nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase)-ROS-p38 MAPK pathway. Thus, our findings provide insights into the use of PMIDA-CoO NPs as antigen delivery vehicles.

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Author information

Authors and Affiliations

  1. Center for Bio-medical Engineering (CBME), Indian Institute of Technology Ropar, Rupnagar, Punjab, India

    Sourav Chattopadhyay

  2. Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal, India

    Somenath Roy

Authors
  1. Sourav Chattopadhyay
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  2. Somenath Roy
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Editors and Affiliations

  1. Department of Biochemistry and Biophysic, University of Kalyani Department of Biochemistry and Biophysic, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Dept of Veterinary Pathobiology, University of Missouri, College Vet, Columbia, MO, USA

    Bimal K Ray

  3. Saroj Gupta Cancer Centre & Research Ins, Kolkata, India

    Sushanta Roychowdhury

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Chattopadhyay, S., Roy, S. (2021). Dynamics of Cobalt Oxide Nanoparticles in the Activation of Reactive Oxygen Species Induced Inflammation and Immunomodulation. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_178-1

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  • DOI: https://doi.org/10.1007/978-981-15-4501-6_178-1

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  • Print ISBN: 978-981-15-4501-6

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