The Crystallinity and Aspect Ratio of Cellulose Nanomaterials Determine Their Pro-Inflammatory and Immune Adjuvant Effects In Vitro and In Vivo

Xiang Wang, Chong Hyun Chang, Jinhong Jiang, Qi Liu, Yu Pei Liao, Jianqin Lu, Linjiang Li, Xiangsheng Liu, Joshua Kim, Ayman Ahmed, André E. Nel, Tian Xia

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Nanocellulose is increasingly considered for applications; however, the fibrillar nature, crystalline phase, and surface reactivity of these high aspect ratio nanomaterials need to be considered for safe biomedical use. Here a comprehensive analysis of the impact of cellulose nanofibrils (CNF) and nanocrystals (CNC) is performed using materials provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences. An intermediary length of nanocrystals is also derived by acid hydrolysis. While all CNFs and CNCs are devoid of cytotoxicity, 210 and 280 nm fluorescein isothiocyanate (FITC)-labeled CNCs show higher cellular uptake than longer and shorter CNCs or CNFs. Moreover, CNCs in the 200–300 nm length scale are more likely to induce lysosomal damage, NLRP3 inflammasome activation, and IL-1β production than CNFs. The pro-inflammatory effects of CNCs are correlated with higher crystallinity index, surface hydroxyl density, and reactive oxygen species generation. In addition, CNFs and CNCs can induce maturation of bone marrow–derived dendritic cells and CNCs (and to a lesser extent CNFs) are found to exert adjuvant effects in ovalbumin (OVA)-injected mice, particularly for 210 and 280 nm CNCs. All considered, the data demonstrate the importance of length scale, crystallinity, and surface reactivity in shaping the innate immune response to nanocellulose.

Original languageEnglish (US)
Article number1901642
JournalSmall
Volume15
Issue number42
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Keywords

  • aspect ratio
  • cellulose nanocrystals
  • cellulose nanofibrils
  • crystallinity
  • humoral immune effects

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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