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Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players

Authors Gurunathan S, Kang MH, Jeyaraj M, Kim JH

Received 21 November 2020

Accepted for publication 31 December 2020

Published 22 January 2021 Volume 2021:16 Pages 515—538

DOI https://doi.org/10.2147/IJN.S291138

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster


Sangiliyandi Gurunathan, Min-Hee Kang, Muniyandi Jeyaraj, Jin-Hoi Kim

Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea

Correspondence: Sangiliyandi Gurunathan; Jin-Hoi Kim
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea
Tel +82 2 450 3687
Fax + 82 2 544 4645
Email gsangiliyandi@yahoo.com; jhkim541@konkuk.ac.kr

Background: Several studies have demonstrated various molecular mechanisms involved in the biogenesis and release of exosomes. However, how external stimuli, such as platinum nanoparticles (PtNPs), induces the biogenesis and release of exosomes remains unclear. To address this, PtNPs were synthesized using lutein to examine their effect on the biogenesis and release of exosomes in human lung epithelial adenocarcinoma cancer cells (A549).
Methods: The size and concentration of isolated exosomes were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis system (NTA). Morphology and structure of exosomes were examined using scanning electron microscopy and transmission electron microscopy (TEM), respectively. Quantification of exosomes were analyzed by EXOCETTM assay and fluorescence polarization (FP). The expression of typical markers of exosomes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).
Results: A549 cells cultured with PtNPs enhance exosome secretion by altering various physiological processes. Interestingly, A549 cells treated with PtNPs increases total protein concentration, biogenesis and release of exosomes associated with PtNPs-induced oxidative stress. GW4869 inhibits PtNPs induced biogenesis and release of exosomes and also acetylcholinesterase (AChE), neutral sphingomyelinase activity (n-SMase), and exosome counts. A549 cells pre-treated with N-acetylcysteine (NAC) significantly inhibited PtNPs induced exosome biogenesis and release. These findings confirmed that PtNPs-induced exosome release was due to the induction of oxidative stress and the ceramide pathway. These factors enhanced exosome biogenesis and release and may be useful in understanding the mechanism of exosome formation, release, and function.
Conclusion: PtNPs provide a promising agent to increase exosome production in A549 cells. These findings offer novel strategies for enhancing exosome release, which can be applied in the treatment and prevention of cancer. Importantly, this is the first study, to our knowledge, showing that PtNPs stimulate exosome biogenesis by inducing oxidative stress and the ceramide pathway.

Keywords: exosome, platinum nanoparticle, cytotoxicity, oxidative stress, acetylcholinesterase activity, neutral sphingomyelinase activity

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