title: Ultrashort Single-Walled Carbon Nanotubes Insert into a Pulmonary Surfactant Monolayer via Self-Rotation: Poration and Mechanical Inhibition.
abstract: It has been widely accepted that longer single-walled carbon nanotubes (SWCNTs) exhibit higher toxicity by causing severe pneumonia once inhaled, yet relatively little is known regarding the potential toxicity of ultrashort SWCNTs, which are of central importance to the development of suitable vehicles for biomedical applications. Here, by combining coarse-grained molecular dynamics (CGMD), pulling simulations, and scaling analysis, we demonstrate that the inhalation toxicity of ultrashort SWCNTs (1.5 nm < l < 5.5 nm) can be derived from the unique behaviors on interaction with the pulmonary surfactant monolayer (PSM), which is located at the air-water interface of alveoli and forms the frontline of the lung host defense. Molecular dynamics (MD) simulations suggest that ultrashort SWCNTs spontaneously insert into the PSM via fast self-rotation. Further translocation toward the water or air phase involves overcoming a high free-energy barrier, indicating that removal of inhaled ultrashort SWCNTs from the PSM is difficult, possibly leading to the accumulation of SWCNTs in the PSM, with prolonged retention and increased inflammation potentials. Under certain conditions, the inserted SWCNTs are found to open hydrophilic pores in the PSM via a mechanism that mimics that of the antimicrobial peptide. Besides, the mechanical property of the PSM is inhibited by the deposited ultrashort SWCNTs through segregation of the inner lipid molecules from the outer phase. Our results bring to the forefront the concern of the inhalation toxicity of ultrashort SWCNTs and provide guidelines for future design of inhaled nanodrug carriers with minimized side effects.
authors.forename: Tongtao
authors.identifier: 0000-0002-8329-167X
authors.initials: T
authors.lastname: Yue
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Shixin
authors.initials: S
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Xianren
authors.identifier: 0000-0002-8026-9012
authors.initials: X
authors.lastname: Zhang
authors.forename: Fang
authors.identifier: 0000-0001-8735-0350
authors.initials: F
authors.lastname: Huang
mesh_terms: D056004:Molecular Dynamics Simulation; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D012399:Rotation
chemical_list: D037742:Nanotubes, Carbon; D011663:Pulmonary Surfactants