{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:18:31Z","timestamp":1787977111989,"version":"build-2784847793"},"reference-count":75,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Isfahan","award":["A\/482\/98"],"award-info":[{"award-number":["A\/482\/98"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Regeneration of the damaged neurons in neurological disorders and returning their activities are two of the main purposes of neuromedicine. Combination use of specific nanoformulations with a therapeutic compound could be a good candidate for neuroregeneration applications. Accordingly, this research aims to utilize the combination of curcumin, as a neurogenesis agent, with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate their effects on PC12 cells\u0374 neuronal branching morphogenesis in the absence of nerve growth factor. Therefore, the effects of each component alone and in combination form on the cytotoxicity, neurogenesis, and neural branching morphogenesis were evaluated using MTT assay, immunofluorescence staining, and inverted microscopy, respectively. Results confirmed the effectiveness of the biocompatible iron oxide nanoparticles (with a size of about 100 nm) in improving the percentage of neural branching (p &lt; 0.01) in PC12 cells. In addition, the combination use of these nanoparticles with curcumin could enhance the effect of curcumin on neurogenesis (p &lt; 0.01). These results suggest that SPIONs in combination with curcumin could act as an inducing factor on PC12 neurogenesis in the absence of nerve growth factor and could offer a novel therapeutic approach to the treatment of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics14122692","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T02:18:06Z","timestamp":1669947486000},"page":"2692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Superparamagnetic Iron Oxide Nanoparticles and Curcumin Equally Promote Neuronal Branching Morphogenesis in the Absence of Nerve Growth Factor in PC12 Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Mahshid","family":"Zarei","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 8174673441, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8844-4591","authenticated-orcid":false,"given":"Abolghasem","family":"Esmaeili","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 8174673441, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0391-1769","authenticated-orcid":false,"given":"Ali","family":"Zarrabi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Zarepour","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1016\/j.biomaterials.2011.01.019","article-title":"Enhancement of neurite outgrowth in PC12 cells by iron oxide nanoparticles","volume":"32","author":"Kim","year":"2011","journal-title":"Biomaterials"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tondo, G., and De Marchi, F. (2022). From Biomarkers to Precision Medicine in Neurodegenerative Diseases: Where Are We?, MDPI.","DOI":"10.3390\/jcm11154515"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1080\/10408398.2020.1865870","article-title":"Polyphenols and neurodegenerative diseases: Focus on neuronal regeneration","volume":"62","author":"Moradi","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/biof.1566","article-title":"Effects of curcumin on mitochondria in neurodegenerative diseases","volume":"46","author":"Bagheri","year":"2020","journal-title":"Biofactors"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neures.2022.05.003","article-title":"Microbiota-gut-brain axis in the Alzheimer\u2019s disease pathology-an overview","volume":"181","author":"Giridharan","year":"2022","journal-title":"Neurosci. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107989","DOI":"10.1016\/j.pharmthera.2021.107989","article-title":"CX3CL1\/CX3CR1 signaling targets for the treatment of neurodegenerative diseases","volume":"231","author":"Subbarayan","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1684\/epd.2021.1406","article-title":"Epilepsy in neurodegenerative diseases","volume":"24","author":"Neri","year":"2022","journal-title":"Epileptic Disord."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., Pinto, M., and Sousa, E. (2018). Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals, 11.","DOI":"10.3390\/ph11020044"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1080\/08820538.2021.1890793","article-title":"Nerve growth factor as an ocular therapy: Applications, challenges, and future directions","volume":"Volume 36","author":"Kanu","year":"2021","journal-title":"Seminars in Ophthalmology"},{"key":"ref_10","first-page":"4726","article-title":"Neuritogenic activity of epigallocatechin gallate and curcumin combination on rat adrenal pheochromocytoma cells","volume":"26","author":"Dikmen","year":"2017","journal-title":"Fresenius Env. Bull"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/biof.1296","article-title":"Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells","volume":"42","author":"Phan","year":"2016","journal-title":"Biofactors"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1900727","DOI":"10.1002\/adma.201900727","article-title":"Efficient delivery of nerve growth factors to the central nervous system for neural regeneration","volume":"31","author":"Xu","year":"2019","journal-title":"Adv. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12951-016-0190-0","article-title":"Iron oxide nanoparticles for neuronal cell applications: Uptake study and magnetic manipulations","volume":"14","author":"Marcus","year":"2016","journal-title":"J. Nanobiotechnol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.4172\/Neuropsychiatry.1000496","article-title":"Modulatory Effects of natural products on neuronal differentiation","volume":"8","author":"An","year":"2018","journal-title":"Neuropsychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1021\/jf203290r","article-title":"Curcuminoids promote neurite outgrowth in PC12 cells through MAPK\/ERK-and PKC-dependent pathways","volume":"60","author":"Liao","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fakhri, S., Pesce, M., Patruno, A., Moradi, S.Z., Iranpanah, A., Farzaei, M.H., and Sobarzo-S\u00e1nchez, E. (2020). Attenuation of Nrf2\/Keap1\/ARE in Alzheimer\u2019s disease by plant secondary metabolites: A mechanistic review. Molecules, 25.","DOI":"10.3390\/molecules25214926"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111119","DOI":"10.1016\/j.biopha.2020.111119","article-title":"The role of curcumin in aging and senescence: Molecular mechanisms","volume":"134","author":"Zia","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16953","DOI":"10.1002\/jcp.28411","article-title":"The impact of curcumin and its modified formulations on Alzheimer\u2019s disease","volume":"234","author":"Farkhondeh","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1080\/10408398.2015.1077195","article-title":"Curcumin, an active component of turmeric (Curcuma longa), and its effects on health","volume":"57","author":"Kocaadam","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1089\/jmf.2016.3889","article-title":"Comparison of the effects of curcumin and RG108 on NGF-induced PC-12 Adh cell differentiation and neurite outgrowth","volume":"20","author":"Dikmen","year":"2017","journal-title":"J. Med. Food"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.2147\/IJN.S208332","article-title":"Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders","volume":"14","author":"Pirzadeh","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cole, G.M., Teter, B., and Frautschy, S.A. (2007). Neuroprotective effects of curcumin. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer.","DOI":"10.1007\/978-0-387-46401-5_8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1254\/jphs.CRJ05010X","article-title":"Use of ginseng in medicine with emphasis on neurodegenerative disorders","volume":"100","author":"Radad","year":"2006","journal-title":"J. Pharmacol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nocito, M.C., De Luca, A., Prestia, F., Avena, P., La Padula, D., Zavaglia, L., Sirianni, R., Casaburi, I., Puoci, F., and Chimento, A. (2021). Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability. Biomedicines, 9.","DOI":"10.3390\/biomedicines9101476"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"589957","DOI":"10.3389\/fchem.2020.589957","article-title":"Application of functional biocompatible nanomaterials to improve curcumin bioavailability","volume":"8","author":"Li","year":"2020","journal-title":"Front. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.2147\/IJN.S328767","article-title":"Emerging trends in nanomaterials for antibacterial applications","volume":"16","author":"Mutalik","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Beyene, A.M., Moniruzzaman, M., Karthikeyan, A., and Min, T. (2021). Curcumin nanoformulations with metal oxide nanomaterials for biomedical applications. Nanomaterials, 11.","DOI":"10.3390\/nano11020460"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sohn, S.-I., Priya, A., Balasubramaniam, B., Muthuramalingam, P., Sivasankar, C., Selvaraj, A., Valliammai, A., Jothi, R., and Pandian, S. (2021). Biomedical applications and bioavailability of curcumin\u2014An updated overview. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122102"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Prasad, S., DuBourdieu, D., Srivastava, A., Kumar, P., and Lall, R. (2021). Metal\u2013Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137094"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Salehi, B., Del Prado-Audelo, M.L., Cort\u00e9s, H., Leyva-G\u00f3mez, G., Stojanovi\u0107-Radi\u0107, Z., Singh, Y.D., Patra, J.K., Das, G., Martins, N., and Martorell, M. (2020). Therapeutic applications of curcumin nanomedicine formulations in cardiovascular diseases. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030746"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s13205-015-0302-9","article-title":"Curcumin nanoparticles: Physico-chemical fabrication and its in vitro efficacy against human pathogens","volume":"5","author":"Pandit","year":"2015","journal-title":"3 Biotech"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.addr.2010.05.006","article-title":"Superparamagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy","volume":"63","author":"Mahmoudi","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","first-page":"541","article-title":"Nanovectors for anticancer agents based on superparamagnetic iron oxide nanoparticles","volume":"2","author":"Marchais","year":"2007","journal-title":"Int. J. Nanomed."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kl\u0119bowski, B., Depciuch, J., Parli\u0144ska-Wojtan, M., and Baran, J. (2018). Applications of noble metal-based nanoparticles in medicine. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124031"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"510","DOI":"10.4236\/jbnb.2011.225062","article-title":"Recent advances in drug delivery systems","volume":"2","author":"Martinho","year":"2011","journal-title":"J. Biomater. Nanobiotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Estelrich, J., and Busquets, M.A. (2021). Magnetic Nanoparticles as Delivery Systems to Penetrate the Blood-Brain Barrier. Nanomedicines for Brain Drug Delivery, Springer.","DOI":"10.1007\/978-1-0716-0838-8_7"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.biomaterials.2014.12.005","article-title":"Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer\u2019s disease mice using magnetic resonance imaging (MRI)","volume":"44","author":"Cheng","year":"2015","journal-title":"Biomaterials"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fncel.2020.00021","article-title":"Application of iron oxide nanoparticles in the diagnosis and treatment of neurodegenerative diseases with emphasis on Alzheimer\u2019s disease","volume":"14","author":"Luo","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.2147\/IJN.S191878","article-title":"Superparamagnetic iron oxide nanoparticles combined with NGF and quercetin promote neuronal branching morphogenesis of PC12 cells","volume":"14","author":"Katebi","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neuro.2012.09.011","article-title":"Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells","volume":"34","author":"Teixeira","year":"2013","journal-title":"Neurotoxicology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1515\/revneuro-2016-0004","article-title":"Phytochemicals as future drugs for Parkinson\u2019s disease: A comprehensive review","volume":"27","author":"Shahpiri","year":"2016","journal-title":"Rev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1039\/C4NR05193A","article-title":"NGF-conjugated iron oxide nanoparticles promote differentiation and outgrowth of PC12 cells","volume":"7","author":"Marcus","year":"2015","journal-title":"Nanoscale"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105723","DOI":"10.1016\/j.foodhyd.2020.105723","article-title":"Casein core-polysaccharide shell nanocomplexes stable at pH 4.5 enabled by chelating and complexation properties of dextran sulfate","volume":"103","author":"Li","year":"2020","journal-title":"Food Hydrocoll."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jtice.2017.11.004","article-title":"Folic acid armed Fe3O4-HPG nanoparticles as a safe nano vehicle for biomedical theranostics","volume":"82","author":"Mostaghasi","year":"2018","journal-title":"J. Taiwan Inst. Chem. Eng."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.bmcl.2008.12.041","article-title":"Curcumin is a potent DNA hypomethylation agent","volume":"19","author":"Liu","year":"2009","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1021\/nn405077y","article-title":"Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer\u2019s disease model via canonical Wnt\/\u03b2-catenin pathway","volume":"8","author":"Tiwari","year":"2014","journal-title":"ACS Nano"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Maiti, P., and Dunbar, G.L. (2018). Use of curcumin, a natural polyphenol for targeting molecular pathways in treating age-related neurodegenerative diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061637"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ijpharm.2016.07.027","article-title":"Bioavailability of curcumin and curcumin glucuronide in the central nervous system of mice after oral delivery of nano-curcumin","volume":"511","author":"Szymusiak","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10571-016-0362-3","article-title":"Reversal of beta-amyloid-induced neurotoxicity in PC12 cells by curcumin, the important role of ROS-mediated signaling and ERK pathway","volume":"37","author":"Fan","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.toxlet.2018.04.033","article-title":"Characterization of superparamagnetic iron oxide nanoparticle-induced apoptosis in PC12 cells and mouse hippocampus and striatum","volume":"292","author":"Liu","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"607","DOI":"10.2174\/1386207324666210705114058","article-title":"Novel drug delivery system for curcumin: Implementation to improve therapeutic efficacy against neurological disorders","volume":"25","author":"Mir","year":"2022","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/biof.1735","article-title":"Curcumin: A small molecule with big functionality against amyloid aggregation in neurodegenerative diseases and type 2 diabetes","volume":"47","author":"Radbakhsh","year":"2021","journal-title":"Biofactors"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Doytchinova, I., Atanasova, M., Salamanova, E., Ivanov, S., and Dimitrov, I. (2020). Curcumin inhibits the primary nucleation of amyloid-beta peptide: A molecular dynamics study. Biomolecules, 10.","DOI":"10.3390\/biom10091323"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5892","DOI":"10.1074\/jbc.M404751200","article-title":"Curcumin inhibits formation of amyloid \u03b2 oligomers and fibrils, binds plaques, and reduces amyloid in vivo","volume":"280","author":"Yang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"742","DOI":"10.4103\/1673-5374.230303","article-title":"Use of curcumin in diagnosis, prevention, and treatment of Alzheimer\u2019s disease","volume":"13","author":"Chen","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.prp.2014.02.005","article-title":"Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson\u2019s disease rat","volume":"210","author":"Yang","year":"2014","journal-title":"Pathol. Res. Pract."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2174\/1570159X19666210823103020","article-title":"PLGA-Based Curcumin Delivery System: An Interesting Therapeutic Approach in the Treatment of Alzheimer\u2019s Disease","volume":"2","author":"Shahbaz","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.2147\/IJN.S165675","article-title":"Impact of nanoparticles on neuron biology: Current research trends","volume":"13","author":"Khan","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"619538","DOI":"10.3389\/fcell.2021.619538","article-title":"Conditional loss of BAF (mSWI\/SNF) scaffolding subunits affects specification and proliferation of oligodendrocyte precursors in developing mouse forebrain","volume":"9","author":"Abbas","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0006-8993(00)02943-7","article-title":"Manganese induces neurite outgrowth in PC12 cells via upregulation of \u03b1v integrins","volume":"885","author":"Lein","year":"2000","journal-title":"Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0161-813X(01)00077-8","article-title":"Mechanisms of manganese-induced rat pheochromocytoma (PC12) cell death and cell differentiation","volume":"23","author":"Roth","year":"2002","journal-title":"Neurotoxicology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S1016-8478(23)13701-0","article-title":"Iron promotes the survival and neurite extension of serum-starved PC12 cells in the presence of NGF by enhancing cell attachment","volume":"15","author":"Hong","year":"2003","journal-title":"Mol. Cells"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/jnr.490340507","article-title":"Manganese induces spreading and process outgrowth in rat pheochromocytoma (PC12) cells","volume":"34","author":"Lin","year":"1993","journal-title":"J. Neurosci. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1039\/C9TB00678H","article-title":"Improved neural differentiation of stem cells mediated by magnetic nanoparticle-based biophysical stimulation","volume":"7","author":"Dai","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"375101","DOI":"10.1088\/1361-6528\/ac7402","article-title":"SPION based magnetic PLGA nanofibers for neural differentiation of mesenchymal stem cells","volume":"33","author":"Mohammadalizadeh","year":"2022","journal-title":"Nanotechnology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1054\/tice.2001.0221","article-title":"Hydroxyl free radicals induce cell differentiation in SK-N-MC neuroblastoma cells","volume":"34","author":"Oravecz","year":"2002","journal-title":"Tissue Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.3402\/nano.v1i0.5358","article-title":"Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION)","volume":"1","author":"Singh","year":"2010","journal-title":"Nano Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-8977-6-1","article-title":"Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling","volume":"6","author":"Apopa","year":"2009","journal-title":"Part. Fibre Toxicol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1046\/j.1365-2443.2003.00663.x","article-title":"The phosphatidylinositol-3 kinase (PI3K)-Akt pathway suppresses neurite branch formation in NGF-treated PC12 cells","volume":"8","author":"Higuchi","year":"2003","journal-title":"Genes Cells"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.biopha.2018.09.106","article-title":"Pharmacotherapy Curcumin loading potentiates the neuroprotective efficacy of Fe3O4 magnetic nanoparticles in cerebellum cells of schizophrenic rats","volume":"108","author":"Naserzadeh","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1039\/D0CS01127D","article-title":"Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine","volume":"50","author":"Susnik","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"203","DOI":"10.4161\/cl.23967","article-title":"Search for inhibitors of endocytosis: Intended specificity and unintended consequences","volume":"2","author":"Dutta","year":"2012","journal-title":"Cell. Logist."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8760","DOI":"10.1039\/c0jm00994f","article-title":"Magnetic nanoparticles: Biomedical applications and challenges","volume":"20","author":"Tran","year":"2010","journal-title":"J. Mater. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nnano.2007.217","article-title":"Targeted delivery of magnetic aerosol droplets to the lung","volume":"2","author":"Dames","year":"2007","journal-title":"Nat. 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