Projects per year
© 2015 Elsevier Ltd. 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.
|Number of pages||17|
|Early online date||9 Oct 2015|
|Publication status||Published - Jan 2016|
FingerprintDive into the research topics of 'Enabling dual cellular destinations of polymeric nanoparticles for treatment following partial injury to the central nervous system'. Together they form a unique fingerprint.
JEOL 2100 TEMCentre for Microscopy, Characterisation & Analysis
Leica TCS SP2 multiphoton confocal microscopeCentre for Microscopy, Characterisation & Analysis
NanoSIMS 50Centre for Microscopy, Characterisation & Analysis
- 2 Finished
Nanotechnology to stop the spread of damage after brain injury
Dunlop, S., Fitzgerald, M., Swaminatha Iyer, K. & Hool, L.
National Health & Medical Research Council NHMRC
1/01/12 → 31/12/14