title: Proteomic profiling of halloysite clay nanotube exposure in intestinal cell co-culture.
abstract: Halloysite is aluminosilicate clay with a hollow tubular structure with nanoscale internal and external diameters. Assessment of halloysite biocompatibility has gained importance in view of its potential application in oral drug delivery. To investigate the effect of halloysite nanotubes on an in vitro model of the large intestine, Caco-2/HT29-MTX cells in monolayer co-culture were exposed to nanotubes for toxicity tests and proteomic analysis. Results indicate that halloysite exhibits a high degree of biocompatibility characterized by an absence of cytotoxicity, in spite of elevated pro-inflammatory cytokine release. Exposure-specific changes in expression were observed among 4081 proteins analyzed. Bioinformatic analysis of differentially expressed protein profiles suggest that halloysite stimulates processes related to cell growth and proliferation, subtle responses to cell infection, irritation and injury, enhanced antioxidant capability, and an overall adaptive response to exposure. These potentially relevant functional effects warrant further investigation in in vivo models and suggest that chronic or bolus occupational exposure to halloysite nanotubes may have unintended outcomes.
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Xianyin
authors.initials: X
authors.lastname: Lai
authors.forename: Mangilal
authors.initials: M
authors.lastname: Agarwal
authors.forename: Yuri M
authors.initials: YM
authors.lastname: Lvov
authors.forename: Chetan
authors.initials: C
authors.lastname: Pachpande
authors.forename: Kody
authors.initials: K
authors.lastname: Varahramyan
authors.forename: Frank A
authors.initials: FA
authors.lastname: Witzmann
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry / Q000633:toxicity*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077215:Clay; D018920:Coculture Techniques; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D043942:Nanotubes / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D013499:Surface Properties
chemical_list: D000538:Aluminum Silicates; D004337:Drug Carriers; D020543:Proteome; D000077215:Clay
keywords: enterocytes; halloysite; intestinal epithelia; label-free quantitative mass spectrometry; proteomics