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Anticancer and immunostimulatory role of encapsulated tumor antigen containing cobalt oxide nanoparticles

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Abstract

The purpose of this study is to evaluate the prospect of using surface modified cobalt oxide(CoO) nanoparticles as carriers of cancerantigens to human macrophages. N-Phosnomethyliminodiacetic acid (PMIDA) was used for surface modification to overcome the toxic effect of CoO nanoparticles. Here, the phosphonate group of the PMIDA acts as a surface-anchoring agent and the remaining –COOH groups bind nonspecifically with tumor associated antigens. This modification allows the conjugation of human oral carcinoma (KB) cell lysate (CL) as an antigen with PMIDA coated CoO nanoparticles (CL–PMIDA–CoO). Particle characterization was performed by dynamic light scattering, atomic force microscopy, and scanning electron microscopy studies. Fourier transform IR spectroscopy was used to investigate conjugation of the protein with nanoparticles. Protein encapsulation was confirmed by protein gel electrophoresis. Active uptake of antigen-conjugated nanoparticles by macrophages was confirmed by fluorescence microscopy. The antitumor activity of the nanocomplex pulsed macrophages was investigated on a human oral carcinoma cell line (KB) in vitro. The modified nanocomplexes upregulate IFN-γ and TNF-α and induce an anticancer immune response by activating macrophages. The use of TNF-α inhibitor confirmed the ability of the CL–PMIDA–CoO nanocomplex to stimulate TNF-α mediated immunostimulation. CL–PMIDA–CoO nanoparticles efficiently increased the CD4+ population. Thus, our findings provide insight into the use of PMIDA coated CoO nanoparticles as antigen delivery vehicles.

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Abbreviations

AFM:

Atomic force microscopy

ASA:

Acetylsalicylic acid

cAMP:

Cyclic adenosine monophosphate

CL:

Cell lysate

CL–PMIDA–CoO:

Cell lysate conjugated N-phosnomethyliminodiacetic acid coated cobalt oxide

COX:

Cyclooxygenase

DC:

Dendritic cell

DLS:

Dynamic light scattering

EDC:

N-Ethyl-N′-(3-dimethylaminopropyl)carbodiimide

FCS:

Fetal calf serum

IFN-γ:

Interferon-γ

iNOS:

Inducible nitric oxide synthase

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NP:

Nanoparticle

PBS:

Phosphate-buffered saline

PMIDA:

N-Phosnomethyliminodiacetic acid

PMIDA–CoO:

N-Phosnomethyliminodiacetic acid coated cobalt oxide

POF:

Pentoxifylline

RBC:

Red blood cell

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

SEM:

Scanning electron microscopy

Th1:

Type 1 T helper

Th2:

Type 2 T helper

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Acknowledgments

The authors express their gratefulness to the Department of Biotechnology, Government of India, for funding. The authors also express their gratefulness to the Indian Institute of Technology, Kharagpur and Vidyasagar University, Midnapore, for providing the facilities to execute these studies.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, 721102, West Bengal, India

    Sourav Chattopadhyay, Sandeep Kumar Dash, Sabyasachi Das, Satyajit Tripathy, Debasis Mandal & Somenath Roy

  2. Department of Chemistry, University of Calcutta, 92 A.P.C Road, Kolkata, 700009, West Bengal, India

    Totan Ghosh & Debasis Das

  3. Nano Materials Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur, West Bengal, India

    Panchanan Pramanik

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  1. Sourav Chattopadhyay
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Correspondence to Somenath Roy.

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Chattopadhyay, S., Dash, S.K., Ghosh, T. et al. Anticancer and immunostimulatory role of encapsulated tumor antigen containing cobalt oxide nanoparticles. J Biol Inorg Chem 18, 957–973 (2013). https://doi.org/10.1007/s00775-013-1044-y

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