title: NGF-conjugated iron oxide nanoparticles promote differentiation and outgrowth of PC12 cells.
abstract: The search for regenerative agents that promote neuronal differentiation and repair is of great importance. Nerve growth factor (NGF) which is an essential contributor to neuronal differentiation has shown high pharmacological potential for the treatment of central neurodegenerative diseases such as Alzheimer's and Parkinson's. However, growth factors undergo rapid degradation, leading to a short biological half-life. In our study, we describe a new nano-based approach to enhance the NGF activity resulting in promoted neuronal differentiation. We covalently conjugated NGF to iron oxide nanoparticles (NGF-NPs) and studied the effect of the novel complex on the differentiation of PC12 cells. We found that the NGF-NP treatment, at the same concentration as free NGF, significantly promoted neurite outgrowth and increased the complexity of the neuronal branching trees. Examination of neuronal differentiation gene markers demonstrated higher levels of expression in PC12 cells treated with the conjugated factor. By manipulating the NGF specific receptor, TrkA, we have demonstrated that NGF-NPs induce cell differentiation via the regular pathway. Importantly, we have shown that NGF-NPs undergo slower degradation than free NGF, extending their half-life and increasing NGF availability. Even a low concentration of conjugated NGF treatment has led to an effective response. We propose the use of the NGF-NP complex which has magnetic characteristics, also as a useful method to enhance NGF efficiency and activity, thus, paving the way for substantial neuronal repair therapeutics.
authors.affiliation: Faculty of Engineering, Bar Ilan University, Ramat Gan 5290002, Israel. orit.shefi@biu.ac.il.
authors.forename: M
authors.initials: M
authors.lastname: Marcus
authors.forename: H
authors.initials: H
authors.lastname: Skaat
authors.forename: N
authors.initials: N
authors.lastname: Alon
authors.forename: S
authors.initials: S
authors.lastname: Margel
authors.forename: O
authors.initials: O
authors.lastname: Shefi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049108:Cell Enlargement / Q000187:drug effects; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D016716:PC12 Cells; D051381:Rats
chemical_list: D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D058726:Nanoconjugates; D009414:Nerve Growth Factors