title: Nanotherapeutics of PTEN Inhibitor with Mesoporous Silica Nanocarrier Effective for Axonal Outgrowth of Adult Neurons.
abstract: Development of therapeutic strategies such as effective drug delivery is an urgent and yet unmet need for repair of damaged nervous systems. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) regulates axonal regrowth of central and peripheral nervous systems; its inhibition, meanwhile, facilitates axonal outgrowth of injured neurons. Here we show that nanotherapeutics based on mesoporous silica nanoparticles loading PTEN-inhibitor bisperoxovanadium (BpV) are effective for delivery of drug molecules and consequent improvement of axonal outgrowth. Mesoporous nanocarriers loaded BpV drug at large amount (27 μg per 1 mg of carrier), and released sustainably over 10 d. Nanocarrier-BpV treatment of primary neurons from the dorsal root ganglions (DRGs) of rats and mice at various concentrations induced them to actively take up the nanocomplexes with an uptake efficiency as high as 85%. The nanocomplex-administered neurons exhibited significantly enhanced axonal outgrowth compared with those treated with free-BpV drug. The expression of a series of proteins involved in PTEN inhibition and downstream signaling was substantially up-/down-regulated by the nanocarrier-BpV system. Injection of the nanocarriers into neural tissues (DRG, brain cortex, and spinal cord), moreover, demonstrated successful integration into neurons, glial cells, oligodendrocytes, and macrophages, suggesting the possible nanotherapeutics applications in vivo. Together, PTEN-inhibitor delivery via mesoporous nanocarriers can be considered a promising strategy for stimulating axonal regeneration in central and peripheral nervous systems.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Fiqi
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Hong-Sun
authors.initials: HS
authors.lastname: Ahn
authors.affiliation: Shriners Hospital's Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine , Philadelphia, Pennsylvania 19140, United States.
authors.forename: Hyukmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Shriners Hospital's Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine , Philadelphia, Pennsylvania 19140, United States.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Jung Keun
authors.initials: JK
authors.lastname: Hyun
mesh_terms: D000818:Animals; D001369:Axons; D005727:Ganglia, Spinal; D051379:Mice; D009457:Neuroglia; D009474:Neurons; D051059:PTEN Phosphohydrolase; D016062:Porosity; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D012822:Silicon Dioxide; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat
keywords: PTEN inhibition; axonal outgrowth; drug delivery; in vivo cellular uptake; mesoporous silica nanoparticles; nanotherapeutics