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Daniel W. Pita-Thomas, Michael Steketee, Jeffrey L. Goldberg, Karl Kador; Functionalized Nanoparticles To Enhance Regenerative Axon Growth. Invest. Ophthalmol. Vis. Sci. 2012;53(14):303.
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Neurons in the central nervous system fail to regenerate their axons after injury. Although there are approaches to neutralize inhibitory signals and add growth-promoting signals, delivery therapeutics to the lesion site is problematic, limiting efficacy. In the present study, we propose use functionalized magnetic nanoparticles (fMNPs) as a treatment delivery system to enhance regenerative axon growth.
We used chemical coupling of fluorescent nanoparticles to agonist anti-trkB antibodies, cholera toxin B and peptides; coculture of retinal ganglion cells (RGCs) with fMNPs to promote endocytosis; and manipulation of the fMNPs using magnetic forces. Intravitreal injection of fMNPs in rats was followed by immunohistochemistry to assess fMNPs’ location.
fMNPs functionalized with different molecules were endocytosed into long-lived signaling endosomes by RGCs and transported along the axon. Application of magnetic forces to cultured RGCs loaded with fMNPs induced changes in axon growth rates. fMNPs injected intravitreally were internalized by RGCs and trafficked to axons in the optic nerve and dendrites in the inner plexiform layer.
fMNPs provide a flexible platform for targeting nano-therapeutics to previously inaccessible regions of the central nervous system and advance our understanding of fundamental mechanisms regulating axon growth.
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