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

• Published in: International journal of nanomedicine Vol. 16; pp. 515 - 538
• Main Authors: Gurunathan, Sangiliyandi, Kang, Min-Hee, Jeyaraj, Muniyandi, Kim, Jin-Hoi
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: A549 Cells; Acetylcholinesterase - metabolism; acetylcholinesterase activity; Acetylcysteine; Acetylcysteine - pharmacology; Adenocarcinoma; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - pathology; Analysis; Aniline Compounds - pharmacology; Apoptosis; Benzylidene Compounds - pharmacology; Biomarkers; Biosynthesis; Cancer; Cancer cells; Cancer therapies; Cell growth; Cell Proliferation - drug effects; Cell Survival - drug effects; Ceramides - metabolism; Cytotoxicity; Enzyme Activation - drug effects; Enzyme-linked immunosorbent assay; exosome; Exosomes - metabolism; Exosomes - ultrastructure; Gene Expression Regulation, Neoplastic - drug effects; Humans; Hypoxia; Kinases; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lutein - pharmacology; Melanoma; Metal Nanoparticles - chemistry; Metal Nanoparticles - ultrastructure; Microscopy; Nanoparticles; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; neutral sphingomyelinase activity; Oncology, Experimental; Original Research; Oxidative stress; Oxidative Stress - drug effects; Particle Size; Physiological aspects; Platinum - pharmacology; platinum nanoparticle; Prevention; Product introduction; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Serum; Sphingomyelin Phosphodiesterase - metabolism; Static Electricity; United States > US; neutral sphingomyelinase activity; platinum nanoparticle; acetylcholinesterase activity; exosome; cytotoxicity; oxidative stress
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S291138

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). 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 EXOCET 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). 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. 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.