Acid-functionalized single-walled carbon nanotubes alter epithelial tight junctions and enhance paracellular permeabilit

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Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)

Acid-functionalized single-walled carbon nanotubes alter epithelial tight junctions and enhance paracellular permeability ANAND P SINGH1,2, , MD. BABU MIA1,  and RAJIV K SAXENA1* 1

Faculty of Life Sciences and Biotechnology, South Asian University, Akbar Bhawan, Chanakyapuri, New Delhi 110 021, India 2

Division of Cardiovascular Disease, University of Alabama-School of Medicine, Birmingham, AL 35233, USA *Corresponding author (Email, [email protected])  

These authors contributed equally to this work.

MS received 12 June 2019; accepted 9 October 2019 Due to their unique properties, carbon nanotubes (CNTs) are being widely explored for industrial and medical applications. This has necessitated a thorough assessment of the effect of CNTs on human and animal physiology and health. Impact of CNTs on epithelial tight junctions has not been evaluated in the context of their toxic effects in many biological systems. In the present study, we examined the effect of acid functionalized single-walled carbon nanotubes (AF-SWCNTs) on the function and expression of two tight junction proteins (ZO-1 and occludin) in the Madin-Darby canine kidney (MDCK) cell line. Treatment of MDCK cells with AF-SWCNT resulted in a downregulation of tight junction proteins, decreased trans-epithelial electrical resistance (TER), increased paracellular permeability, and disruption of tight junctions. Taken together, our data demonstrate that AF-SWCNT disrupts tight junction barrier by downregulating tight junction proteins in MDCK epithelial cells. Keywords. Carbon nanotubes; MDCK; paracellular permeability; tight junctions; transepithelial electrical resistance; ZO-1

1. Introduction In recent years, nanoparticles have emerged as promising probes for multimodal imaging, and also as carriers for targeted drug or gene delivery (Baughman et al. 2002; Bianco et al. 2005). Highvolume production of carbon nanoparticles by the combustion of fuels makes them airborne and pose a potential inhalation health hazard (Aitken et al. 2006; Donaldson et al. 2006; Stern and McNeil 2007). Use of nanoparticles in cosmetics and processing of food and water may result in dermal and oral exposures, respectively (Li et al. 2005; Wang et al. 2006). Therefore, it is of paramount importance to evaluate the potential health hazards associated with exposure to these materials. Previous studies have shown that high doses of single-walled carbon nanotubes (SWCNTs) after inhalation in rodents causes http://www.ias.ac.in/jbiosci

inflammation, epithelioid granulomas, fibrosis in the lungs, blockage of the airways, and cardiotoxicity (Lam et al. 2004; Stern and McNeil 2007). It has been demonstrated that acid functionalization of these particles resulted in highly dispersed suspensions in aqueous media which were more cytotoxic in mouse lung epithelial cell culture assays (Wang et al. 2006; Kumari et al. 2012; Alam et al. 2013). Acid functionalized SWCNTs have also been shown to suppress T-cell act