title: Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy.
abstract: A progressive loss of neuronal structure and function is a signature of many neurodegenerative conditions including chronic traumatic encephalopathy, Parkinson's, Huntington's and Alzheimer's diseases. Mitochondrial dysfunction and oxidative and nitrative stress have been implicated as key pathological mechanisms underlying the neurodegenerative processes. However, current therapeutic approaches targeting oxidative damage are ineffective in preventing the progression of neurodegeneration. Mitochondria-targeted antioxidants were recently shown to alleviate oxidative damage. In this work, we investigated the delivery of biodegradable polyanhydride nanoparticles containing the mitochondria-targeted antioxidant apocynin to neuronal cells and the ability of the nano-formulation to protect cells against oxidative stress. The nano-formulated mitochondria-targeted apocynin provided excellent protection against oxidative stress-induced mitochondrial dysfunction and neuronal damage in a dopaminergic neuronal cell line, mouse primary cortical neurons, and a human mesencephalic cell line. Collectively, our results demonstrate that nano-formulated mitochondria-targeted apocynin may offer improved efficacy of mitochondria-targeted antioxidants to treat neurodegenerative disease.
authors: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA.
authors: Timothy M
authors: TM
authors: Brenza
authors: Department of Biomedical Sciences, Iowa State University, Ames, IA, USA.
authors: Shivani
authors: S
authors: Ghaisas
authors: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA.
authors: Julia E Vela
authors: JEV
authors: Ramirez
authors: Department of Biomedical Sciences, Iowa State University, Ames, IA, USA.
authors: Dilshan
authors: D
authors: Harischandra
authors: Department of Biomedical Sciences, Iowa State University, Ames, IA, USA.
authors: Vellareddy
authors: V
authors: Anantharam
authors: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Balaraman
authors: B
authors: Kalyanaraman
authors: Department of Biomedical Sciences, Iowa State University, Ames, IA, USA. Electronic address: akanthas@iastate.edu.
authors: Anumantha G
authors: AG
authors: Kanthasamy
authors: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA. Electronic address: nbalaji@iastate.edu.
authors: Balaji
authors: B
authors: Narasimhan
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D049388:Polyanhydrides / Q000737:chemistry*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D004337:Drug Carriers; D049388:Polyanhydrides; C056165:acetovanillone
keywords: Mito-apocynin; Neurodegeneration; Oxidative stress; Polyanhydride nanoparticles