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Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma

Abstract

The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining impetus due to the unique biophysical properties of nanoparticles at the quantum level. Silver nanoparticles (AgNPs) have been reported as one type of potent therapeutic nanoparticles. The present study is aimed to determine the effect of AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism. Initially, a bioavailability study showed that mouse serum albumin (MSA)-coated AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10 different doses (1–10 mg/kg b.w.) were performed in LACA mice by measuring the complete blood count, lipid profile and histological parameters. The complete blood count, lipid profile and histological parameter results showed that the doses from 2 to 8 mg (IC50: 6.15 mg/kg b.w.) sequentially increased the count of leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed conclusive toxicity. In an antitumor study, the incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of AgNP-MSA by the sentinel immune cells associated with tumor tissue and a morphologically buckled structure of the immune cells containing AgNP-MSA. Because the toxicity studies revealed a relationship between AgNPs and immune function, the protumorigenic cytokines TNF-α, IL-6 and IL-1β were also assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these cytokines were found to be downregulated after treatment with AgNP-MSA.

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Acknowledgements

We gratefully acknowledge the following organizations and institutes for supporting the work.

1. Department of Biotechnology, Govt. of India for providing the DBT Research Associate fellowship to Dr Biswajit Chakraborty.

2. University Grant Commission, Government of India for providing a doctoral research fellowship to Ramkrishna Pal, Leichombam Mohindro Singh and Dewan Shahidur Rahman.

3. Sophisticated Analytical Instrument Facility, Indian Institute of Technology, Mumbai, India for analyzing the inductively coupled plasmon-atomic emission spectra.

4. Sophisticated Analytical Instrument Facility, North Eastern Hill University, Shillong, Meghalaya, India for TEM analysis.

5. Pasteur Institute, Shillong, Meghalaya, India for providing experimental animals.

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Correspondence to Mahuya Sengupta.

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology’s website. (http://www.nature.com/cmi).

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Chakraborty, B., Pal, R., Ali, M. et al. Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma. Cell Mol Immunol 13, 191–205 (2016). https://doi.org/10.1038/cmi.2015.05

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