Abstract
Despite the increasing use of silver nanoparticles in medical sciences, published studies on their interaction with nerve cells and evaluation of risks are dispersed. This systematic review and meta-analysis could be used to devise safety guidelines for the use of silver nanoparticles in industry and medicine to reduce adverse effects on the CNS.
After extensive searches, the full text of 30 related studies was reviewed and data mining completed. Data were analyzed by calculating the mean of different ratios between treated and untreated groups. Linear regression between variables was evaluated by meta-regression. Subgroup analysis was also performed due to heterogeneity.
Treatment with silver nanoparticles significantly reduced cell viability (SMD = −1.79%; 95% CI: −2.17 to −1.40; p < 0.0001). Concentration > 0.1 μg/mL could kill neurons, while lower concentration would not (SMD −0.258; 95% CI: −0.821 to 0.305; p = 369). In addition to the concentration, the coating, size of the nanoparticles, and cell type are also factors that influence SNP nerve cell toxicity. Measurement of apoptosis (SMD = 2.21; 95% CI: 1.62 to 2.80; p=0.001) and lactate dehydrogenase release rate (SMD = 0.9; 95% CI: 0.33 to 1.47; p < 0.0001) also confirmed the destructive effect of silver nanoparticles on nerve cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ajdary M, Moosavi MA, Rahmati M, Falahati M, Mahboubi M, Mandegary A, Varma RS (2018) Health concerns of various nanoparticles: a review of their in vitro and in vivo toxicity. Nanomaterials 8. https://doi.org/10.3390/nano8090634
Akter M, Sikder MT, Rahman MM, Ullah AKMA, Hossain KFB, Banik S, Kurasaki M (2018) A systematic review on silver nanoparticles-induced cytotoxicity: physicochemical properties and perspectives. J Adv Res 9:1–16. https://doi.org/10.1016/j.jare.2017.10.008
Aziz N, Faraz M, Sherwani MA, Fatma T, Prasad R (2019) Illuminating the Anticancerous efficacy of a new fungal chassis for silver nanoparticle synthesis. Front Chem 7. https://doi.org/10.3389/fchem.2019.00065
Barhoum A, El-Hout SI, Ali GAM, Abu Serea ES, Ibrahim AH, Pal K, Abdelbasir SM (2019) A broad family of carbon nanomaterials: classification, properties, synthesis, and emerging applications. In: Handbook of nanofibers, pp 451–490. https://doi.org/10.1007/978-3-319-53655-2_59
Begum AN, Aguilar JS, Elias L, Hong Y (2016) Silver nanoparticles exhibit coating and dose-dependent neurotoxicity in glutamatergic neurons derived from human embryonic stem cells. Neurotoxicology 57:45–53. https://doi.org/10.1016/j.neuro.2016.08.015
Bin-Meferij MM, Hamida RS (2019) Biofabrication and antitumor activity of silver nanoparticles utilizing novel Nostoc sp. Bahar M. Int J Nanomedicine 14:9019–9029. https://doi.org/10.2147/IJN.S230457
Bonaventura G, La Cognata V, Iemmolo R, Zimbone M, Contino A, Maccarrone G, Cavallaro S (2018) Ag-NPs induce apoptosis, mitochondrial damages and MT3/OSGIN2 expression changes in an in vitro model of human dental-pulp-stem-cells-derived neurons. Neurotoxicology 67:84–93. https://doi.org/10.1016/j.neuro.2018.04.014
Boroumand Z, Golmakani N, Boroumand S (2018) Clinical trials on silver nanoparticles for wound healing. Nanomed J 5(4):186–191. https://doi.org/10.22038/nmj.2018.05.00001
Brandelli A (2019) The interaction of nanostructured antimicrobials with biological systems: cellular uptake, trafficking and potential toxicity. Food Sci Human Wellness. https://doi.org/10.1016/j.fshw.2019.12.003
Braun NJ, Comfort KK, Schlager JJ, Hussain SM (2013) Partial recovery of silver nanoparticle-induced neural cytotoxicity through the application of a static magnetic field. BioNanoScience 3(4):367–377. https://doi.org/10.1007/s12668-013-0109-2
Chen IC, Hsiao IL, Lin HC, Wu CH, Chuang CY, Huang YJ (2016) Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability. Environ Toxicol Pharmacol 47:108–118. https://doi.org/10.1016/j.etap.2016.09.009
Choi JH, Min WK, Gopal J, Lee YM, Muthu M, Chun S, Oh JW (2018) Silver nanoparticle-induced hormesis of astroglioma cells: a Mu-2-related death-inducing protein-orchestrated modus operandi. Int J Biol Macromol 117(2017):1147–1156. https://doi.org/10.1016/j.ijbiomac.2018.05.234
Choo WH, Park CH, Jung SE, Moon B, Ahn H, Ryu JS, Oh SM (2016) Long-term exposures to low doses of silver nanoparticles enhanced in vitro malignant cell transformation in non-tumorigenic BEAS-2B cells. Toxicol In Vitro 37:41–49. https://doi.org/10.1016/j.tiv.2016.09.003
Çiftçi H, Türk M, Tamer U, Karahan S, Menemen Y (2013) Silver nanoparticles: cytotoxic, apoptotic, and necrotic effects on MCF-7 cells. Turk J Biol 37(5):573–581. https://doi.org/10.3906/biy-1302-21
Ferdous Z, Nemmar A (2020) Health impact of silver nanoparticles: a review of the biodistribution and toxicity following various routes of exposure. Int J Mol Sci 21(7):2375
Gajbhiye S, Sakharwade S (2016) Silver nanoparticles in cosmetics. J Cosmetics Dermatol Sci Appl 6(1):48–53. https://doi.org/10.4236/jcdsa.2016.61007
Gao W, Leung SW, Bhushan A, Lai JCK (2014) Cytotoxic effects of silver and gold nanoparticles in human glioblastoma U87 cells. Technical proceedings of the 2014 NSTI nanotechnology conference and expo, NSTI-Nanotech, vol 3, pp 134–137
Gatoo MA, Naseem S, Arfat MY, Mahmood Dar A, Qasim K, Zubair S (2014) Physicochemical properties of nanomaterials: implication in associated toxic manifestations. Biomed Res Int 2014:1–8. https://doi.org/10.1155/2014/498420
George PAB, Kumar N, Abrahamse H, Ray S (2018) Apoptotic efficacy of multifaceted biosynthesized silver nanoparticles on human adenocarcinoma cells. Sci Rep 8. https://doi.org/10.1038/s41598-018-32480-5
Giannossa LC, Longano D, Ditaranto N, Nitti MA, Paladini F, Pollini M, Cioffi N (2013) Metal nanoantimicrobials for textile applications. Nanotechnol Rev 2(3). https://doi.org/10.1515/ntrev-2013-0004
Gonzalez-Carter DA, Leo BF, Ruenraroengsak P, Chen S, Goode AE, Theodorou IG, Porter AE (2017) Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H 2 S-synthesizing enzymes. Sci Rep 7(January):1–14. https://doi.org/10.1038/srep42871
Haase A, Rott S, Mantion A, Graf P, Plendl J, Thünemann AF, Reiser G (2012) Effects of silver nanoparticles on primary mixed neural cell cultures: uptake, oxidative stress and acute calcium responses. Toxicol Sci 126(2):457–468. https://doi.org/10.1093/toxsci/kfs003
Hadrup N, Loeschner K, Mortensen A, Sharma AK, Qvortrup K, Larsen EH, Lam HR (2012) The similar neurotoxic effects of nanoparticulate and ionic silver in vivo and in vitro. Neurotoxicology 33(3):416–423. https://doi.org/10.1016/j.neuro.2012.04.008
Heinz H, Pramanik C, Heinz O, Ding Y, Mishra RK, Marchon D, Ziolo RF (2017) Nanoparticle decoration with surfactants: molecular interactions, assembly, and applications. Surf Sci Rep 72(1):1–58. https://doi.org/10.1016/j.surfrep.2017.02.001
Hsiao IL, Hsieh YK, Chuang CY, Wang CF, Huang YJ (2017) Effects of silver nanoparticles on the interactions of neuron- and glia-like cells: toxicity, uptake mechanisms, and lysosomal tracking. Environ Toxicol 32(6):1742–1753. https://doi.org/10.1002/tox.22397
Jazayeri MH, Amani H, Pourfatollah AA, Pazoki-Toroudi H, Sedighimoghaddam B (2016) Various methods of gold nanoparticles (GNPs) conjugation to antibodies. Sensing Bio-Sensing Res 9:17–22. https://doi.org/10.1016/j.sbsr.2016.04.002
Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK (2018) Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations. Beilstein J Nanotechnol 9(1):1050–1074. https://doi.org/10.3762/bjnano.9.98
Kalantari K, Mostafavi E, Afifi AM, Izadiyan Z, Jahangirian H, Rafiee-Moghaddam R, Webster TJ (2020) Wound dressings functionalized with silver nanoparticles: promises and pitfalls. Nanoscale 12(4):2268–2291. https://doi.org/10.1039/C9NR08234D
Khan AM, Korzeniowska B, Gorshkov V, Tahir M, Schrøder H, Skytte L, Kjeldsen F (2019a) Silver nanoparticle-induced expression of proteins related to oxidative stress and neurodegeneration in an in vitro human blood-brain barrier model. Nanotoxicology 13(2):221–239. https://doi.org/10.1080/17435390.2018.1540728
Khan I, Saeed K, Khan I (2019b) Nanoparticles: properties, applications and toxicities. Arab J Chem 12(7):908–931. https://doi.org/10.1016/j.arabjc.2017.05.011
Kim SH, Ko JW, Koh SK, Lee IC, Son JM, Moon C, Kim JC (2014) Silver nanoparticles induce apoptotic cell death in cultured cerebral cortical neurons. Mol Cell Toxicol 10(2):173–179. https://doi.org/10.1007/s13273-014-0019-6
Lingabathula H, Yellu N (2017) Extra pulmonary toxicity assessment of gold and silver nanorods following intra tracheal instillation in rats. Drug Res 67(10):606–612. https://doi.org/10.1055/s-0043-113255
Liu F, Mahmood M, Xu Y, Watanabe F, Biris AS, Hansen DK, Wang C (2015) Effects of silver nanoparticles on human and rat embryonic neural stem cells. Front Neurosci 9:1–9. https://doi.org/10.3389/fnins.2015.00115
Liu Y, Eaton ED, Wills TE, McCann SK, Antonic A, Howells DW (2018) Human ischaemic cascade studies using SH-SY5Y cells: a systematic review and meta-analysis. Transl Stroke Res 9:564–574. https://doi.org/10.1007/s12975-018-0620-4
Luther EM, Koehler Y, Diendorf J, Epple M, Dringen R (2011) Accumulation of silver nanoparticles by cultured primary brain astrocytes. Nanotechnology 22(37). https://doi.org/10.1088/0957-4484/22/37/375101
Luther EM, Schmidt MM, Diendorf J, Epple M, Dringen R (2012) Upregulation of metallothioneins after exposure of cultured primary astrocytes to silver nanoparticles. Neurochem Res 37(8):1639–1648. https://doi.org/10.1007/s11064-012-0767-4
Ma W, Jing L, Valladares A, Mehta SL, Wang Z, Andy Li P, Bang JJ (2015) Silver nanoparticle exposure induced mitochondrial stress, caspase-3 activation and cell death: amelioration by sodium selenite. Int J Biol Sci 11(8):860–867. https://doi.org/10.7150/ijbs.12059
Mala R, Annie Aglin A, Ruby Celsia AS, Geerthika S, Kiruthika N, VazagaPriya C, Srinivasa Kumar K (2017) Foley catheters functionalised with a synergistic combination of antibiotics and silver nanoparticles resist biofilm formation. IET Nanobiotechnol 11(5):612–620. https://doi.org/10.1049/iet-nbt.2016.0148
Mytych J, Zebrowski J, Lewinska A, Wnuk M (2017) Prolonged effects of silver nanoparticles on p53/p21 pathway-mediated proliferation, DNA damage response, and methylation parameters in HT22 hippocampal neuronal cells. Mol Neurobiol 54(2):1285–1300. https://doi.org/10.1007/s12035-016-9688-6
Neelakandan MS, Thomas S (2018) Applications of silver nanoparticles for medicinal purpose. JSM Nanotechnol Nanomed 6(1):1063. Retrieved from https://www.jscimedcentral.com/Nanotechnology/nanotechnology-6-1063.pdf
Nel A, Xia T, Mädler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627. https://doi.org/10.1126/science.1114397
Nguyen KC, Seligy VL, Massarsky A, Moon TW, Rippstein P, Tan J, Tayabali AF (2013) Comparison of toxicity of uncoated and coated silver nanoparticles. J Phys Conf Ser 429(1). https://doi.org/10.1088/1742-6596/429/1/012025
Oh JH, Son MY, Choi MS, Kim S, Choi AY, Lee HA, Yoon S (2016) Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles. Toxicol Appl Pharmacol 299:8–23. https://doi.org/10.1016/j.taap.2015.11.004
Pavi I, Mili M, Pongrac IM, Brki L, Matijevi T, Ili K, Vinkovi I (2019) Neurotoxicity of silver nanoparticles stabilized with different coating agents: in vitro response of neuronal precursor cells. https://doi.org/10.1016/j.fct.2019.110935
Pongrac IM, Ahmed LB, Mlinarić H, Jurašin DD, Pavičić I, Marjanović Čermak AM, Milić M, Gajović S, Vinković Vrček I (2018) Surface coating affects uptake of silver nanoparticles in neural stem cells. J Trace Elem Med Biol 50:684–692. https://doi.org/10.1016/j.jtemb.2017.12.003
Rai M, Yadav A, Gade A (2009) Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv 27(1):76–83. https://doi.org/10.1016/j.biotechadv.2008.09.002
Rani GN, Rao BN, Shamili M, Jyothi Padmaja I (2018) Combined effect of silver nanoparticles and honey in experimental wound healing process in rats. Biomed Res 29:3074–3078. https://doi.org/10.4066/biomedicalresearch.29-18-898
Repar N, Li H, Aguilar JS, Li QQ, Drobne D, Hong Y (2018) Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived neuron and astrocyte network. Nanotoxicology 12(2):104–116. https://doi.org/10.1080/17435390.2018.1425497
Rohatgi A (2010) WebPlotDigitizer – extract data from plots, images, and maps. Arohatgi. Retrieved from http://arohatgi.info/WebPlotDigitizer/
Rupp ME, Fitzgerald T, Marion N, Helget V, Puumala S, Anderson JR, Fey PD (2004) Effect of silver-coated urinary catheters: efficacy, cost-effectiveness, and antimicrobial resistance. Am J Infect Control 32(8):445–450. https://doi.org/10.1016/j.ajic.2004.05.002
Salazar-García S, Silva-Ramírez AS, Ramirez-Lee MA, Rosas-Hernandez H, Rangel-López E, Castillo CG, Gonzalez C (2015) Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs). J Nanopart Res 17(11):1–13. https://doi.org/10.1007/s11051-015-3257-1
Salvioni L, Galbiati E, Collico V, Alessio G, Avvakumova S, Corsi F, Colombo M (2017) Negatively charged silver nanoparticles with potent antibacterial activity and reduced toxicity for pharmaceutical preparations. Int J Nanomedicine 12:2517–2530. https://doi.org/10.2147/IJN.S127799
Sawicki K, Czajka M, Matysiak-kucharek M, Fal B, Męczyńska-wielgosz S, Sikorska K, Kruszewski M (2019) Toxicity of metallic nanoparticles in the central nervous system. Nanotechnol Rev:175–200
Sharma G, Nam J-S, Sharma AR, Lee S-S (2018) Antimicrobial potential of silver nanoparticles synthesized using medicinal herb coptidis rhizome. Molecules 23(9):2269. https://doi.org/10.3390/molecules23092269
Slavin YN, Asnis J, Häfeli UO, Bach H (2017) Metal nanoparticles: understanding the mechanisms behind antibacterial activity. J Nanobiotechnol 15(1):65. https://doi.org/10.1186/s12951-017-0308-z
Söderstjerna E, Johansson F, Klefbohm B, Englund Johansson U (2013) Gold- and silver nanoparticles affect the growth characteristics of human embryonic neural precursor cells. PLoS One 8(3):1–13. https://doi.org/10.1371/journal.pone.0058211
Söderstjerna E, Bauer P, Cedervall T, Abdshill H, Johansson F, Johansson UE (2014) Silver and gold nanoparticles exposure to in vitro cultured retina – studies on nanoparticle internalization, apoptosis, oxidative stress, glial- and microglial activity. PLoS One 9(8). https://doi.org/10.1371/journal.pone.0105359
Soleimani M, Habibi-Pirkoohi M (2017) Biosynthesis of silver nanoparticles using Chlorella vulgaris and evaluation of the antibacterial efficacy against Staphylococcus aureus. Avicenna J Med Biotechnol 9:120–125
Stensberg MC, Wei Q, Mclamore ES, Marshall D, Wei A, Porterfield DM, Sepulveda MS (2012) Toxicological studies on silver nanoparticles. Nanomedicine (Lond) 6(5):879–898. https://doi.org/10.2217/nnm.11.78.Toxicological
Strużyńska L, Skalska J (2018) Mechanisms underlying neurotoxicity of silver nanoparticles. Cell Mol Toxicol Nanoparticles 1048:227–250
Sun C, Yin N, Wen R, Liu W, Jia Y, Hu L, Jiang G (2016) Silver nanoparticles induced neurotoxicity through oxidative stress in rat cerebral astrocytes is distinct from the effects of silver ions. Neurotoxicology 52:210–221. https://doi.org/10.1016/j.neuro.2015.09.007
Tejada S, Manayi A, Daglia M, Nabavi SF, Sureda A, Hajheydari Z, Nabavi SM (2016) Wound healing effects of curcumin: a short review. Curr Pharm Biotechnol 17(11):1002–1007. https://doi.org/10.2174/1389201017666160721123109
Thiruvengadam M, Rajakumar G, Chung I-M (2018) Nanotechnology: current uses and future applications in the food industry. 3 Biotech 8(1):74. https://doi.org/10.1007/s13205-018-1104-7
Tuncsoy BS (2018) Toxicity of nanoparticles on insects: a review. Adana Bilim ve Teknoloji Üniversitesi Fen Bilimleri Dergisi 1(2):49–61. Retrieved from https://dergipark.org.tr/download/article-file/614363
Wang R, Song B, Wu J, Zhang Y, Chen A, Shao L (2018) Potential adverse effects of nanoparticles on the reproductive system. Int J Nanomedicine 13:8487–8506. https://doi.org/10.2147/IJN.S170723
Wennersten R, Fidler J, Spitsyna A (2008) Nanotechnology: a new technological revolution in the 21st century. In: Handbook of performability engineering, pp 943–952. https://doi.org/10.1007/978-1-84800-131-2_57
Yang Z, Liu ZW, Allaker RP, Reip P, Oxford J, Ahmad Z, Ren G (2010) A review of nanoparticle functionality and toxicity on the central nervous system. J R Soc Interface 7:S411–S422. https://doi.org/10.1098/rsif.2010.0158.focus
Yang X, Gondikas AP, Marinakos SM, Auffan M, Liu J, Hsu-Kim H, Meyer JN (2012) Mechanism of silver nanoparticle toxicity is dependent on dissolved silver and surface coating in caenorhabditis elegans. Environ Sci Technol 46:1119–1127. https://doi.org/10.1021/es202417t
Yesilot S, Aydin C (2019) Silver nanoparticles; a new hope in cancer therapy? Eastern J Med 24(1):111–116. https://doi.org/10.5505/ejm.2019.66487
Yin N, Liu Q, Liu J, He B, Cui L, Li Z, Jiang G (2013) Silver nanoparticle exposure attenuates the viability of rat cerebellum granule cells through apoptosis coupled to oxidative stress. Small 9:1831–1841. https://doi.org/10.1002/smll.201202732
Yin N, Hu B, Yang R, Liang S, Liang S, Faiola F (2018) Assessment of the developmental neurotoxicity of silver nanoparticles and silver ions with mouse embryonic stem cells in vitro. J Interdiscip Nanomed 3(3):133–145. https://doi.org/10.1002/jin2.49
Yuan YG, Zhang S, Hwang JY, Kong IK (2018) Silver nanoparticles potentiates cytotoxicity and apoptotic potential of camptothecin in human cervical cancer cells. Oxid Med Cell Longev 2018. https://doi.org/10.1155/2018/6121328
Zhang T, Wang L, Chen Q, Chen C (2014) Cytotoxic potential of silver nanoparticles. Yonsei Med J 55:283–291. https://doi.org/10.3349/ymj.2014.55.2.283
Zhu B, Li Y, Lin Z, Zhao M, Xu T, Wang C, Deng N (2016) Silver nanoparticles induce HePG-2 cells apoptosis through ROS-mediated signaling pathways. Nanoscale Res Lett 11. https://doi.org/10.1186/s11671-016-1419-4
Ziemińska E, Stafiej A, Struzyńska L (2014) The role of the glutamatergic NMDA receptor in nanosilver-evoked neurotoxicity in primary cultures of cerebellar granule cells. Toxicology 315(1):38–48. https://doi.org/10.1016/j.tox.2013.11.008
Declarations
Funding FR was supported by IRAN University of Medical Sciences, Grants 97-3-75-13323.
MRH was supported by US NIH Grants R01AI050875 and R21AI121700.
Conflicts of Interest/Competing Interests MRH declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc., Cleveland, OH; BeWell Global Inc., Wan Chai, Hong Kong; Hologenix Inc. Santa Monica, CA; LumiThera Inc., Poulsbo, WA; Vielight, Toronto, Canada; Bright Photomedicine, Sao Paulo, Brazil; Quantum Dynamics LLC, Cambridge, MA; Global Photon Inc., Bee Cave, TX; Medical Coherence, Boston MA; NeuroThera, Newark DE; JOOVV Inc., Minneapolis-St. Paul MN; AIRx Medical, Pleasanton CA; FIR Industries, Inc. Ramsey, NJ; UVLRx Therapeutics, Oldsmar, FL; Ultralux UV Inc., Lansing MI; Illumiheal & Petthera, Shoreline, WA; MB Lasertherapy, Houston, TX; ARRC LED, San Clemente, CA; Varuna Biomedical Corp. Incline Village, NV; Niraxx Light Therapeutics, Inc., Boston, MA. Consulting; Lexington Int, Boca Raton, FL; USHIO Corp, Japan; Merck KGaA, Darmstadt, Germany; Philips Electronics Nederland B.V. Eindhoven, Netherlands; Johnson & Johnson Inc., Philadelphia, PA; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. Stockholdings: Global Photon Inc., Bee Cave, TX; Mitonix, Newark, DE.
Availability of Data and Material The data that support the findings of this study are available from the corresponding author (FR) on request.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Janzadeh, A. et al. (2021). The Toxic Effect of Silver Nanoparticles on Nerve Cells: A Systematic Review and Meta-Analysis. In: de Voogt, P. (eds) Reviews of Environmental Contamination and Toxicology Volume 257. Reviews of Environmental Contamination and Toxicology, vol 257. Springer, Cham. https://doi.org/10.1007/398_2021_67
Download citation
DOI: https://doi.org/10.1007/398_2021_67
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-88216-7
Online ISBN: 978-3-030-88217-4
eBook Packages: Earth and Environmental ScienceEarth and Environmental Science (R0)