Enabling dual cellular destinations of polymeric nanoparticles for treatment following partial injury to the central nervous system

I. Lozić, R. V. Hartz, C. A. Bartlett, J. A. Shaw, M. Archer, P. S.R. Naidu, N. M. Smith, S. A. Dunlop, K. Swaminathan Iyer, M. R. Kilburn, M. Fitzgerald

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Following neurotrauma, oxidative stress is spread via the astrocytic syncytium and is associated with increased aquaporin 4 (AQP4), inflammatory cell infiltration, loss of neurons and glia and functional deficits. Herein we evaluate multimodal polymeric nanoparticles functionalized with an antibody to an extracellular epitope of AQP4, for targeted delivery of an anti-oxidant as a therapeutic strategy following partial optic nerve transection. Using fluorescence microscopy, spectrophotometry, correlative nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy, in vitro and in vivo, we demonstrate that functionalized nanoparticles are coated with serum proteins such as albumin and enter both macrophages and astrocytes when administered to the site of a partial optic nerve transection in rat. Antibody functionalized nanoparticles synthesized to deliver the antioxidant resveratrol are effective in reducing oxidative damage to DNA, AQP4 immunoreactivity and preserving visual function. Non-functionalized nanoparticles evade macrophages more effectively and are found more diffusely, including in astrocytes, however they do not preserve the optic nerve from oxidative damage or functional loss following injury. Our study highlights the need to comprehensively investigate nanoparticle location, interactions and effects, both in vitro and in vivo, in order to fully understand functional outcomes.

Original languageEnglish
Pages (from-to)200-216
Number of pages17
JournalBiomaterials
Volume74
DOIs
Publication statusPublished - Jan 2016
Externally publishedYes

Keywords

  • Central nervous system injury
  • Macrophages
  • Nanoscale secondary ion mass spectroscopy (NanoSIMS)
  • Oxidative stress and aquaporin 4
  • Polymer nanoparticles
  • Targeted drug delivery of antioxidants

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