{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:13:10Z","timestamp":1780593190764,"version":"3.54.1"},"reference-count":92,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T00:00:00Z","timestamp":1546732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG6G0491"],"award-info":[{"award-number":["CMRPG6G0491"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG6H0501"],"award-info":[{"award-number":["CMRPG6H0501"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem\/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF for the induction of neural differentiation in induced pleuripotent stem cells (iPSCs), where tween 80 (T80) and superparamagnetic iron oxide (SPIO) were added for central nervous system (CNS) targeting and magnetic resonance (MR) image tracking, respectively. Both methods by which the BDNF was carried resulted in loading efficiencies greater than 95%. The nanoparticle-mediated delivery of BDNF resulted in neural differentiation of iPSCs detected on immunofluorescence staining as early as 7 days, with enhanced differentiation efficiency by 1.3-fold compared to the control on flow cytometry; the delivery system of surface-adsorbed BDNF gave rise to cells that had the best neural development than the encapsulated formulation. T80-coating disrupted the in vitro blood\u2013brain barrier model with a corresponding 1.5- to two-fold increase in permeability. SPIO-loaded PBCA NPs exhibited a concentration-dependent, rapid decay in signal intensity on the phantom MR experiment. This study demonstrates the versatility of the PBCA NP, and the surface-adsorption of BDNF is the preferred method of delivery for the differentiation of iPSCs.<\/jats:p>","DOI":"10.3390\/ijms20010182","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T03:06:06Z","timestamp":1547003166000},"page":"182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Comparison between Polybutylcyanoacrylate Nanoparticles with Either Surface-Adsorbed or Encapsulated Brain-Derived Neurotrophic Factor on the Neural Differentiation of iPSCs"],"prefix":"10.3390","volume":"20","author":[{"given":"Martin Hsiu-Chu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiu-Yen","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Tai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jih-Chao","family":"Yeh","sequence":"additional","affiliation":[{"name":"Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"Department of Urology at the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsong-Hai","family":"Lee","sequence":"additional","affiliation":[{"name":"Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-7764","authenticated-orcid":false,"given":"Ming-Hsueh","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Neng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Tsung","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-1-4614-2098-9_12","article-title":"Great promise of tissue-resident adult stem\/progenitor cells in transplantation and cancer therapies","volume":"741","author":"Mimeault","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3389\/fncel.2015.00383","article-title":"Meninges harbor cells expressing neural precursor markers during development and adulthood","volume":"9","author":"Bifari","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1002\/glia.22579","article-title":"The adult spinal cord harbors a population of GFAP-positive progenitors with limited self-renewal potential","volume":"61","author":"Fiorelli","year":"2013","journal-title":"GLIA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1006\/mcne.1996.0595","article-title":"The adult rat hippocampus contains primordial neural stem cells","volume":"8","author":"Palmer","year":"1996","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1523\/JNEUROSCI.22-02-00437.2002","article-title":"Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents","volume":"22","author":"Gritti","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nm837","article-title":"Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain","volume":"9","author":"Nunes","year":"2003","journal-title":"Nat. Med."},{"key":"ref_7","first-page":"163","article-title":"Neural regeneration","volume":"367","author":"Steward","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrn2591","article-title":"The bright side of the glial scar in CNS repair","volume":"10","author":"Rolls","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nature17623","article-title":"Astrocyte scar formation aids central nervous system axon regeneration","volume":"532","author":"Anderson","year":"2016","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1098\/rstb.2006.1887","article-title":"Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells","volume":"361","author":"Sohur","year":"2006","journal-title":"Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13632","DOI":"10.1073\/pnas.2234031100","article-title":"Inflammation is detrimental for neurogenesis in adult brain","volume":"100","author":"Ekdahl","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.stem.2011.03.010","article-title":"Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus","volume":"8","author":"Encinas","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1474-9726.2011.00694.x","article-title":"Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells","volume":"10","author":"Bernal","year":"2011","journal-title":"Aging Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s12974-016-0667-7","article-title":"Metabolic determinants of the immune modulatory function of neural stem cells","volume":"13","author":"Drago","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.5966\/sctm.2015-0068","article-title":"Subcutaneous transplantation of neural precursor cells in experimental autoimmune encephalomyelitis reduces chemotactic signals in the central nervous system","volume":"4","author":"Ravanidis","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1111\/j.1582-4934.2011.01259.x","article-title":"Intracerebral transplantation of foetal neural stem cells improves brain dysfunction induced by intracerebral haemorrhage stroke in mice","volume":"15","author":"Wang","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1242\/dev.092551","article-title":"Induced pluripotent stem cells in medicine and biology","volume":"140","author":"Takahashi","year":"2013","journal-title":"Development"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.stem.2013.11.014","article-title":"An effective approach to prevent immune rejection of human ESC-derived allografts","volume":"14","author":"Rong","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1089\/scd.2011.0649","article-title":"Induced pluripotent stem cell consensus genes: Implication for the risk of tumorigenesis and cancers in induced pluripotent stem cell therapy","volume":"21","author":"Zhang","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"883","DOI":"10.3727\/096368910X539092","article-title":"Tumorigenic development of induced pluripotent stem cells in ischemic mouse brain","volume":"20","author":"Yamashita","year":"2011","journal-title":"Cell Transpl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.5732\/cjc.012.10065","article-title":"The propensity for tumorigenesis in human induced pluripotent stem cells is related with genomic instability","volume":"32","author":"Liang","year":"2013","journal-title":"Chin. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.stemcr.2015.02.016","article-title":"Elimination of tumorigenic human pluripotent stem cells by a recombinant lectin-toxin fusion protein","volume":"4","author":"Tateno","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"116","DOI":"10.4252\/wjsc.v7.i1.116","article-title":"Methods of induced pluripotent stem cells for clinical application","volume":"7","author":"Seki","year":"2015","journal-title":"World J. Stem Cells"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"694","DOI":"10.5966\/sctm.2015-0017","article-title":"Tumor-Free Transplantation of Patient-Derived Induced Pluripotent Stem Cell Progeny for Customized Islet Regeneration","volume":"5","author":"Ohmine","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nature07677","article-title":"Induced pluripotent stem cells from a spinal muscular atrophy patient","volume":"457","author":"Ebert","year":"2009","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1073\/pnas.0910012107","article-title":"Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency","volume":"107","author":"Hu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1002\/jnr.21669","article-title":"Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK\/ERK and PI3K\/Akt-dependent signaling pathways","volume":"86","author":"Lim","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1523\/JNEUROSCI.20-09-03221.2000","article-title":"Brain-derived neurotrophic factor differentially regulates excitatory and inhibitory synaptic transmission in hippocampal cultures","volume":"20","author":"Bolton","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2016.04.006","article-title":"BDNF promotes the axonal regrowth after sciatic nerve crush through intrinsic neuronal capability upregulation and distal portion protection","volume":"621","author":"Zheng","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1046\/j.1460-9568.2000.00078.x","article-title":"Polysorbate-80 coating enhances uptake of polybutylcyanoacrylate (PBCA)-nanoparticles by human and bovine primary brain capillary endothelial cells","volume":"12","author":"Ramge","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18837","DOI":"10.1073\/pnas.1111405108","article-title":"Nanoparticles enhance brain delivery of blood\u2013brain barrier-impermeable probes for in vivo optical and magnetic resonance imaging","volume":"108","author":"Koffie","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","first-page":"149254","article-title":"Cationic polybutyl cyanoacrylate nanoparticles for DNA delivery","volume":"2009","author":"Duan","year":"2009","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1080\/10611860903112842","article-title":"Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles","volume":"17","author":"Kurakhmaeva","year":"2009","journal-title":"J. Drug Target."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1007\/s12031-014-0438-9","article-title":"Protective Effects of Poly (butyl) Cyanoacrylate Nanoparticles Containing Vasoactive Intestinal Peptide Against 6-Hydroxydopamine-Induced Neurotoxicity In Vitro","volume":"55","author":"Xu","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_36","first-page":"445","article-title":"Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles","volume":"6","author":"Tian","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3109\/1061186X.2015.1020426","article-title":"Polybutylcyanoacrylate nanocarriers as promising targeted drug delivery systems","volume":"23","author":"Gao","year":"2015","journal-title":"J. Drug Target."},{"key":"ref_38","first-page":"1291","article-title":"Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles","volume":"10","author":"Cabeza","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_39","first-page":"6433","article-title":"Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(Butylcyanoacrylate) nanoparticles","volume":"9","author":"Melguizo","year":"2015","journal-title":"Drug Des. Dev. Therapy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jconrel.2014.11.005","article-title":"Nanotoxicity of poly(n-butylcyano-acrylate) nanoparticles at the blood-brain barrier, in human whole blood and in vivo","volume":"197","author":"Kolter","year":"2015","journal-title":"J. Controll. Release"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0006-8993(95)00023-J","article-title":"Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles)","volume":"674","author":"Kreuter","year":"1995","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.jmbbm.2017.01.003","article-title":"Polymerization kinetics of n-butyl cyanoacrylate glues used for vascular embolization","volume":"69","author":"Li","year":"2017","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"587608","DOI":"10.1155\/2013\/587608","article-title":"A randomized clinical trial comparing the effect of different haemostatic agents for haemostasis of the liver after hepatic resection","volume":"2013","author":"Kakaei","year":"2013","journal-title":"HPB Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s00405-007-0454-2","article-title":"The use of cyanoacrylates for wound closure in head and neck surgery","volume":"265","author":"Bozkurt","year":"2008","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1177\/15910199000060S129","article-title":"Embolization of Arteriovenous Malformation with Diluted Mixture of NBCA","volume":"6","author":"Tamatani","year":"2000","journal-title":"Int. Neuroradiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12951-015-0156-7","article-title":"Cellular uptake and intracellular degradation of poly(alkyl cyanoacrylate) nanoparticles","volume":"14","author":"Sulheim","year":"2016","journal-title":"J. Nanobiotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0141-3910(02)00113-1","article-title":"Hydrolysis of poly (n-butylcyanoacrylate) nanoparticles using esterase","volume":"78","author":"Birkinshaw","year":"2002","journal-title":"Polym. Degrad. Stab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11095-011-0510-x","article-title":"Opsonization, biodistribution, cellular uptake and apoptosis study of PEGylated PBCA nanoparticle as potential drug delivery carrier","volume":"29","author":"Chaudhari","year":"2012","journal-title":"Pharm. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.brainres.2008.01.039","article-title":"Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer\u2019s disease","volume":"1200","author":"Wilson","year":"2008","journal-title":"Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The blood-brain barrier: An overview: Structure, regulation, and clinical implications","volume":"16","author":"Ballabh","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1208\/s12249-015-0287-z","article-title":"Targeting Therapeutics Across the Blood Brain Barrier (BBB), Prerequisite Towards Thrombolytic Therapy for Cerebrovascular Disorders\u2014An Overview and Advancements","volume":"16","author":"Pulicherla","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1177\/0271678X16630991","article-title":"In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use","volume":"36","author":"Helms","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.brainres.2009.01.011","article-title":"Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a brain tumor model","volume":"1261","author":"Wang","year":"2009","journal-title":"Brain Res."},{"key":"ref_54","first-page":"3921","article-title":"Poly(n-butylcyanoacrylate) nanoparticles for oral delivery of quercetin: Preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats","volume":"10","author":"Bagad","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.ejpb.2008.05.007","article-title":"Delivery of nanoparticles to the brain detected by fluorescence microscopy","volume":"70","author":"Reimold","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/mp900306x","article-title":"ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: Study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model","volume":"7","author":"Mulik","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/(SICI)1099-1263(199905\/06)19:3<163::AID-JAT561>3.0.CO;2-H","article-title":"Comparison of cytotoxicity of various surfactants tested on normal human fibroblast cultures using the neutral red test, MTT assay and LDH release","volume":"19","author":"Arechabala","year":"1999","journal-title":"J. Appl. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2007.02.091","article-title":"A functional in vitro model of rat blood-brain barrier for molecular analysis of efflux transporters","volume":"1150","author":"Perriere","year":"2007","journal-title":"Brain Res."},{"key":"ref_59","first-page":"e51278","article-title":"Setting-up an in vitro model of rat blood-brain barrier (BBB): A focus on BBB impermeability and receptor-mediated transport","volume":"28","author":"Molino","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_60","first-page":"307","article-title":"An overview of in vitro techniques for blood-brain barrier studies","volume":"89","author":"Reichel","year":"2003","journal-title":"Methods Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1113\/jphysiol.1990.sp018243","article-title":"Electrical resistance across the blood-brain barrier in anaesthetized rats: A developmental study","volume":"429","author":"Butt","year":"1990","journal-title":"J. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1038\/srep04160","article-title":"A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources","volume":"4","author":"Lippmann","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.bbrc.2011.01.110","article-title":"Transport of Poly(n-butylcyano-acrylate) nanoparticles across the blood-brain barrier in vitro and their influence on barrier integrity","volume":"406","author":"Rempe","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1023\/A:1022604120952","article-title":"Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles","volume":"20","author":"Kreuter","year":"2003","journal-title":"Pharm. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1021\/jm501535r","article-title":"CNS Drug Design: Balancing Physicochemical Properties for Optimal Brain Exposure","volume":"58","author":"Rankovic","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fneng.2013.00007","article-title":"The blood-brain barrier: An engineering perspective","volume":"6","author":"Wong","year":"2013","journal-title":"Front. Neuroeng."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jconrel.2016.05.044","article-title":"Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases","volume":"235","author":"Saraiva","year":"2016","journal-title":"J. Controll. Release"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.colsurfb.2009.11.006","article-title":"Electrophoresis of human brain microvascular endothelial cells with uptake of cationic solid lipid nanoparticles: Effect of surfactant composition","volume":"76","author":"Kuo","year":"2010","journal-title":"Colloids Surf. B"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1016\/j.biomaterials.2007.07.029","article-title":"Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential","volume":"28","author":"Patil","year":"2007","journal-title":"Biomaterials"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s13726-012-0027-0","article-title":"Fabrication and characterization of a new MRI contrast agent based on a magnetic dextran\u2013spermine nanoparticle system","volume":"21","author":"Zabara","year":"2012","journal-title":"Iran. Polym. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"86","DOI":"10.7150\/thno.4006","article-title":"Improving the magnetic resonance imaging contrast and detection methods with engineered magnetic nanoparticles","volume":"2","author":"Huang","year":"2012","journal-title":"Theranostics"},{"key":"ref_72","first-page":"1727","article-title":"Nanoparticles in magnetic resonance imaging: From simple to dual contrast agents","volume":"10","author":"Estelrich","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12951-018-0375-9","article-title":"Magnetic field distribution modulation of intrathecal delivered ketorolac iron-oxide nanoparticle conjugates produce excellent analgesia for chronic inflammatory pain","volume":"16","author":"Wu","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s11033-014-3020-1","article-title":"Comparison of different protocols for neural differentiation of human induced pluripotent stem cells","volume":"41","author":"Salimi","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.scr.2011.12.001","article-title":"Neural differentiation of patient specific iPS cells as a novel approach to study the pathophysiology of multiple sclerosis","volume":"8","author":"Song","year":"2012","journal-title":"Stem Cell Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.1038\/s41598-017-03519-w","article-title":"Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule","volume":"7","author":"Cao","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1756-6606-5-17","article-title":"Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington\u2019s disease patient cells","volume":"5","author":"Juopperi","year":"2012","journal-title":"Mol. Brain"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.stemcr.2016.08.012","article-title":"Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and alpha-Synuclein Accumulation","volume":"7","author":"Chung","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e106952","DOI":"10.1371\/journal.pone.0106952","article-title":"Dual small-molecule targeting of SMAD signaling stimulates human induced pluripotent stem cells toward neural lineages","volume":"9","author":"Wattanapanitch","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6626","DOI":"10.1038\/ncomms7626","article-title":"Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells","volume":"6","author":"Du","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1515\/revneuro-2012-0042","article-title":"Inducible pluripotent stem cells for the treatment of ischemic stroke: Current status and problems","volume":"23","author":"Zhu","year":"2012","journal-title":"Rev. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nbt.1529","article-title":"Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling","volume":"27","author":"Chambers","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_83","first-page":"54900","article-title":"Rapid Neuronal Differentiation of Induced Pluripotent Stem Cells for Measuring Network Activity on Micro-electrode Arrays","volume":"119","author":"Frega","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"760","DOI":"10.15252\/msb.20145508","article-title":"Rapid neurogenesis through transcriptional activation in human stem cells","volume":"10","author":"Busskamp","year":"2014","journal-title":"Mol. Syst. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neuron.2013.05.029","article-title":"Rapid single-step induction of functional neurons from human pluripotent stem cells","volume":"78","author":"Zhang","year":"2013","journal-title":"Neuron"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1101\/gad.841400","article-title":"Neurotrophins: Key regulators of cell fate and cell shape in the vertebrate nervous system","volume":"14","author":"Bibel","year":"2000","journal-title":"Genes Dev."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chung, C.Y., Lin, M.H., Lee, I.N., Lee, T.H., Lee, M.H., and Yang, J.T. (2017). Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030663"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0959-4388(00)00208-7","article-title":"Trk receptors: Mediators of neurotrophin action","volume":"11","author":"Patapoutian","year":"2001","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"18430","DOI":"10.1073\/pnas.1115907108","article-title":"Self-amplifying autocrine actions of BDNF in axon development","volume":"108","author":"Cheng","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","first-page":"265","article-title":"Nanoencapsulation for drug delivery","volume":"13","author":"Kumari","year":"2014","journal-title":"EXCLI J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijpharm.2004.11.025","article-title":"Loading efficiency of stavudine on polybutylcyanoacrylate and methylmethacrylate- sulfopropylmethacrylate copolymer nanoparticles","volume":"290","author":"Kuo","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9717","DOI":"10.1016\/j.biomaterials.2013.08.083","article-title":"Polybutylcyanoacrylate nanoparticles for delivering hormone response element-conjugated neurotrophin-3 to the brain of intracerebral hemorrhagic rats","volume":"34","author":"Chung","year":"2013","journal-title":"Biomaterials"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/182\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:23:50Z","timestamp":1760185430000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,6]]},"references-count":92,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["ijms20010182"],"URL":"https:\/\/doi.org\/10.3390\/ijms20010182","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,6]]}}}