Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice

Furong Tian, Nunja C. Habel, Renfu Yin, Stephanie Hirn, Atrayee Banerjee, Nuran Ercal, Shinji Takenaka, Giovani Estrada, Kostas Kostarelos, Wolfgang Kreyling, Tobias Stoeger

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Carbon nanotubes (CNTs) represent promising vectors to facilitate cellular drug delivery and to overcome biological barriers, but some types may also elicit persistent pulmonary inflammation based on their fibre characteristics. Here, we show the pulmonary response to aqueous suspensions of block copolymer dispersed, double-walled carbon nanotubes (DWCNT, length 1-10 μm) in mice by bronchoalveolar lavage (BAL) analysis, and BAL and blood cytokine and lung antioxidant profiling. The intratracheally instilled dose of 50 μg DWCNT caused significant pulmonary inflammation that was not resolved during a 7-day observation period. Light microscopy investigation of the uptake of DWCNT agglomerates revealed no particle ingestion for granulocytes, but only for macrophages. Accumulating macrophage, multinucleated macrophage and lymphocyte numbers in the alveolar region further indicated ineffective resolution with chronification of the inflammation. The local inflammatory impairment of the lung was accompanied by pulmonary antioxidant depletion and haematological signs of systemic inflammation. While the observed inflammation during its acute phase was dominated by neutrophils and neutrophil recruiting cytokines, the contribution of macrophages and lymphocytes with related cytokines became more significant after day 3 of exposure. This study confirms that acute pulmonary toxicity can occur on exposure of high doses of DWCNT agglomerates and offers further insight for improved nanotube design parameters to avoid potential long-term toxicity. © 2013 Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)412-420
    Number of pages8
    JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
    Volume84
    Issue number2
    DOIs
    Publication statusPublished - Jun 2013

    Keywords

    • Carbon nanotubes
    • Cytokines
    • DWCNT
    • Glutathione
    • Phagocytosis
    • Pulmonary inflammation
    • Systemic inflammation

    Fingerprint

    Dive into the research topics of 'Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice'. Together they form a unique fingerprint.

    Cite this