Skip to main content

Advertisement

SpringerLink
Log in

Nanotechnology in neurosurgery: a systematic review

  • Review Article
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Background

The application of nanotechnology in medicine encompasses an interdisciplinary field of sciences for the diagnosis, treatment, and monitoring of medical conditions. This study aims to systematically review and summarize the advances of nanotechnology applicable to neurosurgery.

Methods

We performed a PubMed advanced search of reports exploring the advances of nanotechnology and nanomedicine relating to diagnosis, treatment, or both, in neurosurgery, for the last decade. The search was performed according to PRISMA guidelines, and the following data were extracted from each paper: title; authors; article type; PMID; DOI; year of publication; in vitro, in vivo model; nanomedical, nanotechnological material; nanofield; neurosurgical field; the application of the system; and main conclusions of the study.

Results

A total of 78 original studies were included in this review. The results were organized into the following categories: functional neurosurgery, head trauma, neurodegenerative diseases, neuro-oncology, spinal surgery and peripheral nerves, vascular neurosurgery, and studies that apply to more than one field. A further categorization applied in terms of nanomedical field such as neuroimaging, neuro-nanotechnology, neuroregeneration, theranostics, and neuro-nanotherapy.

Conclusion

In reviewing the literature, significant advances in imaging and treatment of central nervous system diseases are underway and are expected to reach clinical practice in the next decade by the application of the rapidly evolving nanotechnology techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Absar S, Choi S, Ahsan F, Cobos E, Yang VC, Kwon YM (2013) Preparation and characterization of anionic oligopeptide-modified tissue plasminogen activator for triggered delivery: an approach for localized thrombolysis. Thromb Res. 131(3):e91–e99

    Article  CAS  PubMed  Google Scholar 

  2. Aly AE, Harmon B, Padegimas L, Sesenoglu-Laird O, Cooper MJ, Yurek DM et al (2019) Intranasal delivery of hGDNF plasmid DNA nanoparticles results in long-term and widespread transfection of perivascular cells in rat brain. Nanomedicine. 16:20–33

    Article  CAS  PubMed  Google Scholar 

  3. Andrychowski J, Frontczak-Baniewicz M, Sulejczak D, Kowalczyk T, Chmielewski T, Czernicki Z et al (2013) Nanofiber nets in prevention of cicatrization in spinal procedures. Experimental study. Folia Neuropathol. 51(2):147–157

    Article  PubMed  Google Scholar 

  4. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R et al (2017) Heart Disease and Stroke Statistics-2017 update: a report from the American Heart Association. Circulation. 135(10):e146–e603

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bouras A, Kaluzova M, Hadjipanayis CG (2015) Radiosensitivity enhancement of radioresistant glioblastoma by epidermal growth factor receptor antibody-conjugated iron-oxide nanoparticles. J Neurooncol. 124(1):13–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cao L, Duan PG, Li XL, Yuan FL, Zhao MD, Che W et al (2012) Biomechanical stability of a bioabsorbable self-retaining polylactic acid/nano-sized beta-tricalcium phosphate cervical spine interbody fusion device in single-level anterior cervical discectomy and fusion sheep models. Int J Nanomedicine 7:5875–5880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen YC, Chiang CF, Chen LF, Liao SC, Hsieh WY, Lin WL (2014) Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic and imaging agents into brain tissues. Biomaterials. 35(6):2051–2065

    Article  CAS  PubMed  Google Scholar 

  8. Christie C, Madsen SJ, Peng Q, Hirschberg H (2015) Macrophages as nanoparticle delivery vectors for photothermal therapy of brain tumors. Ther Deliv. 6(3):371–384

    Article  CAS  PubMed  Google Scholar 

  9. Chuapoco MR, Choy M, Schmid F, Duffy BA, Lee HJ, Lee JH (2019) Carbon monofilament electrodes for unit recording and functional MRI in same subjects. Neuroimage. 186:806–816

    Article  CAS  PubMed  Google Scholar 

  10. Clarke JL, Molinaro AM, Cabrera JR, DeSilva AA, Rabbitt JE, Prey J et al (2017) A phase 1 trial of intravenous liposomal irinotecan in patients with recurrent high-grade glioma. Cancer Chemother Pharmacol. 79(3):603–610

    Article  CAS  PubMed  Google Scholar 

  11. Coluccia D, Figueiredo CA, Wu MY, Riemenschneider AN, Diaz R, Luck A et al (2018) Enhancing glioblastoma treatment using cisplatin-gold-nanoparticle conjugates and targeted delivery with magnetic resonance-guided focused ultrasound. Nanomedicine. 14(4):1137–1148

    Article  CAS  PubMed  Google Scholar 

  12. Diaz RJ, McVeigh PZ, O’Reilly MA, Burrell K, Bebenek M, Smith C et al (2014) Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: potential for targeting experimental brain tumors. Nanomedicine. 10(5):1075–1087

    Article  CAS  PubMed  Google Scholar 

  13. Dosa E, Tuladhar S, Muldoon LL, Hamilton BE, Rooney WD, Neuwelt EA (2011) MRI using ferumoxytol improves the visualization of central nervous system vascular malformations. Stroke. 42(6):1581–1588

    Article  PubMed  PubMed Central  Google Scholar 

  14. Evans TM, Van Remmen H, Purkar A, Mahesula S, Gelfond JA, Sabia M et al (2014) Microwave & magnetic (M(2)) proteomics of a mouse model of mild traumatic brain injury. Transl Proteom. 3:10–21

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Faucher L, Guay-Begin AA, Lagueux J, Cote MF, Petitclerc E, Fortin MA (2011) Ultra-small gadolinium oxide nanoparticles to image brain cancer cells in vivo with MRI. Contrast Media Mol Imaging. 6(4):209–218

    CAS  PubMed  Google Scholar 

  16. Favate AS, Younger DS (2016) Epidemiology of ischemic stroke. Neurol Clin. 34(4):967–980

    Article  PubMed  Google Scholar 

  17. Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V (2009) Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 8(4):355–369

    Article  PubMed  Google Scholar 

  18. Freitas RA Jr (2005) What is nanomedicine? Nanomedicine 1(1):2–9

    Article  CAS  PubMed  Google Scholar 

  19. Girasole G, Muro G, Mintz A, Chertoff J (2013) Transforaminal lumbar interbody fusion rates in patients using a novel titanium implant and demineralized cancellous allograft bone sponge. Int J Spine Surg. 7(1):e95–e100

    Article  PubMed  PubMed Central  Google Scholar 

  20. Grannan BL, Yanamadala V, Venteicher AS, Walcott BP, Barr JC (2014) Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci. 21(10):1819–1821

    Article  PubMed  Google Scholar 

  21. Hadjipanayis CG, Machaidze R, Kaluzova M, Wang L, Schuette AJ, Chen H et al (2010) EGFRvIII antibody-conjugated iron oxide nanoparticles for magnetic resonance imaging-guided convection-enhanced delivery and targeted therapy of glioblastoma. Cancer Res. 70(15):6303–6312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL et al (2015) Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14(4):388–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Holtzman DM, Morris JC, Goate AM (2011) Alzheimer’s disease: the challenge of the second century. Sci Transl Med 3(77):77sr1

    Article  PubMed  PubMed Central  Google Scholar 

  24. Huang N, Cheng S, Zhang X, Tian Q, Pi J, Tang J et al (2017) Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood-brain barrier and targeted fluorescence imaging of glioma and tumor vasculature. Nanomedicine. 13(1):83–93

    Article  CAS  PubMed  Google Scholar 

  25. Inayathullah M, Tan A, Jeyaraj R, Lam J, Cho NJ, Liu CW et al (2016) Self-assembly and sequence length dependence on nanofibrils of polyglutamine peptides. Neuropeptides. 57:71–83

    Article  CAS  PubMed  Google Scholar 

  26. Ji D, Xu N, Liu Z, Shi Z, Low SS, Liu J et al (2019) Smartphone-based differential pulse amperometry system for real-time monitoring of levodopa with carbon nanotubes and gold nanoparticles modified screen-printing electrodes. Biosens Bioelectron. 129:216–223

    Article  CAS  PubMed  Google Scholar 

  27. Kaluzova M, Bouras A, Machaidze R, Hadjipanayis CG (2015) Targeted therapy of glioblastoma stem-like cells and tumor non-stem cells using cetuximab-conjugated iron-oxide nanoparticles. Oncotarget. 6(11):8788–8806

    Article  PubMed  PubMed Central  Google Scholar 

  28. Katzenschlager R, Hughes A, Evans A, Manson AJ, Hoffman M, Swinn L et al (2005) Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson’s disease: a prospective study using single-dose challenges. Mov Disord. 20(2):151–157

    Article  PubMed  Google Scholar 

  29. Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP et al (2018) Graphene quantum dots prevent alpha-synucleinopathy in Parkinson’s disease. Nat Nanotechnol. 13(9):812–818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ko J, Hemphill M, Yang Z, Sewell E, Na YJ, Sandsmark DK et al (2018) Diagnosis of traumatic brain injury using miRNA signatures in nanomagnetically isolated brain-derived extracellular vesicles. Lab Chip. 18(23):3617–3630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kuijten MM, Hannah Degeling M, Chen JW, Wojtkiewicz G, Waterman P, Weissleder R et al (2015) Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging. Sci Rep. 5:17220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lee SS, Hsu EL, Mendoza M, Ghodasra J, Nickoli MS, Ashtekar A et al (2015) Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis. Adv Healthc Mater. 4(1):131–141

    Article  CAS  PubMed  Google Scholar 

  33. Lin CY, Hsieh HY, Chen CM, Wu SR, Tsai CH, Huang CY et al (2016) Non-invasive, neuron-specific gene therapy by focused ultrasound-induced blood-brain barrier opening in Parkinson’s disease mouse model. J Control Release. 235:72–81

    Article  CAS  PubMed  Google Scholar 

  34. Lin CY, Li RJ, Huang CY, Wei KC, Chen PY (2018) Controlled release of liposome-encapsulated temozolomide for brain tumour treatment by convection-enhanced delivery. J Drug Target. 26(4):325–332

    Article  CAS  PubMed  Google Scholar 

  35. Lin CY, Tsai CH, Feng LY, Chai WY, Lin CJ, Huang CY et al (2019) Focused ultrasound-induced blood brain-barrier opening enhanced vascular permeability for GDNF delivery in Huntington’s disease mouse model. Brain Stimul. 12(5):1143–1150

    Article  PubMed  Google Scholar 

  36. Liu Y, Ai K, Ji X, Askhatova D, Du R, Lu L et al (2017) Comprehensive insights into the multi-antioxidative mechanisms of melanin nanoparticles and their application to protect brain from injury in ischemic stroke. J Am Chem Soc. 139(2):856–862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu G, Shen H, Mao J, Zhang L, Jiang Z, Sun T et al (2013) Transferrin modified graphene oxide for glioma-targeted drug delivery: in vitro and in vivo evaluations. ACS Appl Mater Interfaces. 5(15):6909–6914

    Article  CAS  PubMed  Google Scholar 

  38. Liu MX, Zhong J, Dou NN, Visocchi M, Gao G (2017) One-pot aqueous synthesization of near-infrared quantum dots for bioimaging and photodynamic therapy of gliomas. Acta Neurochir Suppl. 124:303–308

    Article  PubMed  Google Scholar 

  39. Liu Y, Zhou H, Yin T, Gong Y, Yuan G, Chen L et al (2019) Quercetin-modified gold-palladium nanoparticles as a potential autophagy inducer for the treatment of Alzheimer's disease. J Colloid Interface Sci. 552:388–400

    Article  CAS  PubMed  Google Scholar 

  40. Mangraviti A, Tzeng SY, Kozielski KL, Wang Y, Jin Y, Gullotti D et al (2015) Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo. ACS Nano. 9(2):1236–1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mendiburu-Elicabe M, Gil-Ranedo J (2015) Combination therapy of intraperitoneal rapamycin and convection-enhanced delivery of nanoliposomal CPT-11 in rodent orthotopic brain tumor xenografts. Curr Cancer Drug Targets. 15(4):352–362

    Article  CAS  PubMed  Google Scholar 

  42. Minami SS, Sun B, Popat K, Kauppinen T, Pleiss M, Zhou Y et al (2012) Selective targeting of microglia by quantum dots. J Neuroinflammation. 9:22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mochel F, Barritault J, Boldieu N, Eugene M, Sedel F, Durr A et al (2007) Contribution of in vitro NMR spectroscopy to metabolic and neurodegenerative disorders. Rev Neurol (Paris). 163(10):960–965

    Article  CAS  PubMed  Google Scholar 

  44. Mokarram N, Dymanus K, Srinivasan A, Lyon JG, Tipton J, Chu J et al (2017) Immunoengineering nerve repair. Proc Natl Acad Sci U S A. 114(26):E5077–E5E84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mooney R, Roma L, Zhao D, Van Haute D, Garcia E, Kim SU et al (2014) Neural stem cell-mediated intratumoral delivery of gold nanorods improves photothermal therapy. ACS Nano. 8(12):12450–12460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Olmez I, Love S, Xiao A, Manigat L, Randolph P, McKenna BD et al (2018) Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha. Neuro Oncol. 20(2):192–202

    Article  CAS  PubMed  Google Scholar 

  47. Patil R, Portilla-Arias J, Ding H, Konda B, Rekechenetskiy A, Inoue S et al (2012) Cellular delivery of doxorubicin via pH-controlled hydrazone linkage using multifunctional nano vehicle based on poly(beta-l-malic acid). Int J Mol Sci. 13(9):11681–11693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rutka JT, Kim B, Etame A, Diaz RJ (2014) Nanosurgical resection of malignant brain tumors: beyond the cutting edge. ACS Nano. 8(10):9716–9722

    Article  CAS  PubMed  Google Scholar 

  49. Saboori P, Walker G (2019) Brain injury and impact characteristics. Ann Biomed Eng. 47(9):1982–1992

    Article  PubMed  Google Scholar 

  50. Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F (2012) New pharmacological strategies for treatment of Alzheimer’s disease: focus on disease modifying drugs. Br J Clin Pharmacol. 73(4):504–517

    Article  CAS  PubMed  Google Scholar 

  51. Sayour EJ, Grippin A, De Leon G, Stover B, Rahman M, Karachi A et al (2018) Personalized tumor RNA loaded lipid-nanoparticles prime the systemic and intratumoral milieu for response to cancer immunotherapy. Nano Lett. 18(10):6195–6206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Schiariti MP, Restelli F, Ferroli P, Benetti A, Berenzi A, Ferri A et al (2017) Fibronectin-adherent peripheral blood derived mononuclear cells as Paclitaxel carriers for glioblastoma treatment: an in vitro study. Cytotherapy. 19(6):721–734

    Article  CAS  PubMed  Google Scholar 

  53. Schneider CS, Perez JG, Cheng E, Zhang C, Mastorakos P, Hanes J et al (2015) Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells. Biomaterials. 42:42–51

    Article  CAS  PubMed  Google Scholar 

  54. Shevtsov MA, Nikolaev BP, Yakovleva LY, Parr MA, Marchenko YY, Eliseev I, et al. (2015) 70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma. J Control Release. 220(Pt A):329–40.

  55. Shimbo D, Abumiya T, Kurisu K, Osanai T, Shichinohe H, Nakayama N et al (2017) Superior microvascular perfusion of infused liposome-encapsulated hemoglobin prior to reductions in infarctions after transient focal cerebral ischemia. J Stroke Cerebrovasc Dis. 26(12):2994–3003

    Article  PubMed  Google Scholar 

  56. Sonuc Karaboga MN, Sezginturk MK (2019) Cerebrospinal fluid levels of alpha-synuclein measured using a poly-glutamic acid-modified gold nanoparticle-doped disposable neuro-biosensor system. Analyst. 144(2):611–621

    Article  CAS  PubMed  Google Scholar 

  57. Sun G, Wei D, Liu X, Chen Y, Li M, He D, Zhong J (2013) Novel biodegradable electrospun nanofibrous P(DLLA-CL) balloons for the treatment of vertebral compression fractures. Nanomedicine. 9(6):829–838

    Article  CAS  PubMed  Google Scholar 

  58. Tysnes OB, Storstein A (2017) Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 124(8):901–905

    Article  PubMed  Google Scholar 

  59. Valdes PA, Jacobs V, Harris BT, Wilson BC, Leblond F, Paulsen KD et al (2015) Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery. J Neurosurg. 123(3):771–780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Veiseh O, Gunn JW, Kievit FM, Sun C, Fang C, Lee JS et al (2009) Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles. Small. 5(2):256–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang T, Kievit FM, Veiseh O, Arami H, Stephen ZR, Fang C et al (2013) Targeted cell uptake of a noninternalizing antibody through conjugation to iron oxide nanoparticles in primary central nervous system lymphoma. World Neurosurg. 80(1–2):134–141

    Article  PubMed  Google Scholar 

  62. Wang Y, Meng Y, Wang S, Li C, Shi W, Chen J et al (2015) Direct solvent-derived polymer-coated nitrogen-doped carbon nanodots with high water solubility for targeted fluorescence imaging of glioma. Small. 11(29):3575–3581

    Article  CAS  PubMed  Google Scholar 

  63. Xi G, Robinson E, Mania-Farnell B, Vanin EF, Shim KW, Takao T et al (2014) Convection-enhanced delivery of nanodiamond drug delivery platforms for intracranial tumor treatment. Nanomedicine. 10(2):381–391

    Article  CAS  PubMed  Google Scholar 

  64. Yang W, Barth RF, Wu G, Huo T, Tjarks W, Ciesielski M et al (2009) Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors. J Neurooncol. 95(3):355–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yi GQ, Gu B, Chen LK (2014) The safety and efficacy of magnetic nano-iron hyperthermia therapy on rat brain glioma. Tumour Biol. 35(3):2445–2449

    Article  CAS  PubMed  Google Scholar 

  66. Zhao G, Huang Q, Wang F, Zhang X, Hu J, Tan Y et al (2018) Targeted shRNA-loaded liposome complex combined with focused ultrasound for blood brain barrier disruption and suppressing glioma growth. Cancer Lett. 418:147–158

    Article  CAS  PubMed  Google Scholar 

  67. Zhao M, Li A, Chang J, Fu X, Zhang Z, Yan R et al (2013) Develop a novel superparamagnetic nano-carrier for drug delivery to brain glioma. Drug Deliv. 20(3–4):95–101

    Article  CAS  PubMed  Google Scholar 

  68. Zhu W, Masood F, O’Brien J, Zhang LG (2015) Highly aligned nanocomposite scaffolds by electrospinning and electrospraying for neural tissue regeneration. Nanomedicine. 11(3):693–704

    Article  CAS  PubMed  Google Scholar 

  69. Zhu X, Ni S, Xia T, Yao Q, Li H, Wang B et al (2015) Anti-neoplastic cytotoxicity of SN-38-loaded PCL/gelatin electrospun composite nanofiber scaffolds against human glioblastoma cells in vitro. J Pharm Sci. 104(12):4345–4354

    Article  CAS  PubMed  Google Scholar 

  70. Zhu L, Zhao Z, Cheng P, He Z, Cheng Z, Peng J et al (2017) Antibody-mimetic peptoid nanosheet for label-free serum-based diagnosis of Alzheimer’s disease. Adv Mater. 29(30)

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, “Evangelismos” Hospital, Athens, Greece

    Dimitrios Giakoumettis

  2. Department of Neurosurgery, Medical School, National and “Kapodistrian” University of Athens, Athens, Greece

    Dimitrios Giakoumettis & Spyros Sgouros

  3. Department of Pediatric Neurosurgery, “Iaso” Children’s Hospital, Kifisias Avenue 37-39, 151 23 Marousi, Athens, Greece

    Spyros Sgouros

Authors
  1. Dimitrios Giakoumettis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Spyros Sgouros
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Spyros Sgouros.

Ethics declarations

For this type of study, formal consent is not required. This article does not contain any studies with human participants performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giakoumettis, D., Sgouros, S. Nanotechnology in neurosurgery: a systematic review. Childs Nerv Syst 37, 1045–1054 (2021). https://doi.org/10.1007/s00381-020-05008-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-020-05008-4

Keywords

Search

Navigation