Abstract
The beginning of the twenty-first century saw advancements in all areas of life, including medicine and nanotechnology. This review will look at the most recent advances in nanomaterials for diagnostics and treatments. The emphasis is on the application of nanofibers, nanosensors, and quantum dots (QDs) in medication delivery, neuron regeneration, chemical detection, and microelectrode probes. The manufacture of implantable nanofibers and nanosensors based on QDs, and their application-specific features impacting the interface with targeted brain cells were described. The collaborative efforts have helped us to understand the potential of nanostructured materials in fabrication to overcome the limits of micro and bulk materials in treatments and diagnostics. These advancements will eventually lead to using nanostructures, including nanofibers and nanosensors, in high throughput cutting-edge applications. Only when extensive safety investigations have been completed may the use of nanomaterials on an industrial basis be viable.
Graphical abstract
This review discusses the recent advances in the usage of nanostructures and nanoparticles (NPs) for diagnostics and treatments, with a special focus on nanofibers, nanosensors, and quantum dots (QDs) applications in drug delivery, nerve regeneration, chemical detection, and microelectrode probes.












Similar content being viewed by others
References
Shi J, Votruba AR, Farokhzad OC, Langer R (2010) Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Lett 10(9):3223–3230. https://doi.org/10.1021/nl102184c
Miller SJ, Philips T, Kim N, Dastgheyb R et al (2019) Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin. Nature Neurosci 22(5):741. https://doi.org/10.1038/s41593-019-0366-7
Gilmore JL, Yi X, Quan L, Kabanov AV (2008) Novel nanomaterials for clinical neuroscience. J. Neuroimmune Pharmacol 3(2):83–94. https://doi.org/10.1007/s11481-007-9099-6
Saeid K, Ramakrishna S, Mozafari M (2019) Chemistry of biomaterials: future prospects. Curr Opin Biomed Eng 10:181–190. https://doi.org/10.1016/j.cobme.2019.07.003
Moser E, Moser MB (2014) Mapping your every move. Cerebrum: the Dana forum on brain science. 2014: 25009694. https://doi.org/10.7554/eLife.27041.001
Angle MR, Cui B, Melosh NA (2015) Nanotechnology and neurophysiology. Curr Opin Neurobiol 32:132–140. https://doi.org/10.1016/j.conb.2015.03.014
Kumar A, Tan A, Wong J, Spagnoli JC, Lam J, Blevins BD, Natasha G, Thorne L, Ashkan K, Xie J, Liu H (2017) Nanotechnology for neuroscience: promising approaches for diagnostics, therapeutics and brain activity mapping. Adv Funct Mater 27(39):1700489. https://doi.org/10.1002/adfm.201700489
Das S, Carnicer-Lombarte A, Fawcett JW, Bora U (2016) Bio-inspired nano tools for neuroscience. Prog Neurobiol 142:1–22. https://doi.org/10.1016/j.pneurobio.2016.04.008
Alexander A, Siddique S, Ajazuddin S, Shehata AM, Shaker MA, Rahman SAU, Iqbal M, Abdul M, Shaker MA (2019) Nanotechnology: a non-invasive diagnosis and therapeutic tool for brain disorders. Afr J Pharm Pharmacol 13(10):118–123. https://doi.org/10.5897/AJPP2019.5008
Amunts K, Ebell C, Muller J, Telefont M, Knoll A, Lippert T (2016) The human brain project: creating a European research infrastructure to decode the human brain. Neuron 92(3):574–581. https://doi.org/10.1016/j.neuron.2016.10.046
Shahjouei S, Sadeghi-Naini M, Yang Z, Kobeissy F, Rathore D, Shokraneh F, Wang KK (2018) The diagnostic values of UCH-L1 in traumatic brain injury: a meta-analysis. Brain Inj 32(1):1–17. https://doi.org/10.1080/02699052.2017.1382717
Yang X, McGlynn E, Das R, Paşca SP, Cui B, Heidari H (2021) Nanotechnology enables novel modalities for neuromodulation. Adv Mater 33(52):2103208. https://doi.org/10.1002/adma.202103208
Hansen J T, Koeppen BM (2002) Netter’s atlas of human physiology 249. ICON
Suh WH, Suslick KS, Stucky GD, Suh YH (2009) Nanotechnology, nanotoxicology, and neuroscience. Prog Neurobiol 87(3):133–170. https://doi.org/10.1016/j.pneurobio.2008.09.009
Kang M, Jung S, Zhang H, Kang T, Kang H, Yoo Y, Kim B (2014) Subcellular neural probes from single-crystal gold nanowires. ACS Nano 8(8):8182–8189. https://doi.org/10.1021/nn5024522
Liu Q, Zhao C, Chen M, Liu Y, Zhao Z, Wu F, Zhou C (2020) Flexible multiplexed In2O3 nanoribbon aptamer-field-effect transistors for biosensing. Iscience 23(9):10146. https://doi.org/10.1016/j.isci.2020.101469
Zhang W, Huang Z, Pu X, Chen X, Yin G, Wang L, Gao F (2020) Fabrication of doxorubicin and chlorotoxin-linked Eu-Gd2O3 nanorods with dual-model imaging and targeted therapy of brain tumor. Chin Chem Lett 31(1):285–291. https://doi.org/10.1016/j.cclet.2019.04.018
Saleh MY, Prajapati N, DeCoster MA, Lvov Y (2020) Tagged halloysite nanotubes as a carrier for intercellular delivery in brain microvascular endothelium. Front Bioeng Biotechnol 8:451. https://doi.org/10.3389/fbioe.2020.00451
Yan H, Wang L, Wang J, Weng X, Lei H, Wang X, Li C (2012) Two-order targeted brain tumor imaging by using an optical/paramagnetic nanoprobe across the blood brain barrier. ACS Nano 6(1):410–420. https://doi.org/10.1021/nn203749v
Kreuter J, Ramge P, Petrov V, Hamm S, Gelperina SE, Engelhardt B, Begley DJ (2003) 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. Pharm Res 20:409–416. https://doi.org/10.1023/A:1022604120952
Liu L, Venkatraman SS, Yang YY, Guo K, Lu J, He B, Moochhala S, Kan L (2008) Polymeric micelles anchored with TAT for delivery of antibiotics across the blood–brain barrier. Peptide Sci 90:617–623. https://doi.org/10.1002/bip.20998
Baklaushev VP, Nukolova NN, Khalansky AS et al (2015) Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1. Drug Deliv 22:276–285. https://doi.org/10.3109/10717544.2013.876460
Xia H, Gao X, Gu G, Liu Z, Zeng N, Hu Q, Chen J (2011) Low molecular weight protamine-functionalized nanoparticles for drug delivery to the brain after intranasal administration. Biomaterials 32:9888–9898. https://doi.org/10.1016/j.biomaterials.2011.09.004
Katare YK, Daya RP, Sookram Gray C, Luckham RE, Bhandari J, Chauhan AS, Mishra RK (2015) Brain targeting of a water insoluble antipsychotic drug haloperidol via the intranasal route using PAMAM dendrimer. Mol Pharmaceut 12:3380–3388. https://doi.org/10.1021/acs.molpharmaceut.5b00402
Neuwelt EA, Várallyay P, Bagó AG, Muldoon LL, Nesbit G, Nixon R (2004) Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumours. Neuropathol Appl Neurobiol 30:456–471. https://doi.org/10.1111/j.1365-2990.2004.00557.x
Kim SG, Harel N, Jin T, Kim T, Lee P, Zhao F (2013) Cerebral blood volume MRI with intravascular superparamagnetic iron oxide nanoparticles. NMR Biomed 26:949–962. https://doi.org/10.1002/nbm.2885
Hainfeld JF, Smilowitz HM, O’Connor MJ, Dilmanian FA, Slatkin DN (2013) Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine 8(10):1601–1609. https://doi.org/10.2217/nnm.12.165
Miladi I, Alric C, Dufort S, Mowat P et al (2014) The in vivo radiosensitizing effect of gold nanoparticles based MRI contrast agents. Small 10:1116–1124. https://doi.org/10.1002/smll.201302303
Wu QL, Xu HL, Xiong C, Lan QH, Fang ML, Cai JH, Lu CT (2020) c (RGDyk)-modified nanoparticles encapsulating quantum dots as a stable fluorescence probe for imaging-guided surgical resection of glioma under the auxiliary UTMD. Artif Cells Nanomed Biotechnol 48(1):143–158. https://doi.org/10.1080/21691401.2019.1699821
Bini TB, Gao S, Wang S, Ramakrishna S (2006) Poly (l-lactide-co-glycolide) biodegradable microfibers and electrospun nanofibers for nerve tissue engineering: an in vitro study. J Mater Sci 41:6453–6459. https://doi.org/10.1007/s10853-006-0714-3
Thompson ZS, Rijal NP, Jarvis D, Edwards A, Bhattarai N (2016) Synthesis of keratin-based nanofiber for biomedical engineering. JoVE 108:e53381. https://doi.org/10.3791/53381
Maryam R, Mozafari M (2018) Protein adsorption on polymers. Mater Today Commun 17:527–540. https://doi.org/10.1016/j.mtcomm.2018.10.024
Guo Y, Werner CF, Canales A, Yu L, Jia X, Anikeeva P, Yoshinobu T (2020) Polymer-fiber-coupled field-effect sensors for label-free deep brain recordings. PLoS ONE 15:e0228076. https://doi.org/10.1371/journal.pone.0228076
Rodthongkum N, Ruecha N, Rangkupan R, Vachet RW, Chailapakul O (2013) Graphene-loaded nanofiber-modified electrodes for the ultrasensitive determination of dopamine. Anal Chim Acta 804:84–91. https://doi.org/10.1016/j.aca.2013.09.057
Khan MQ, Kharaghani D, Nishat N, Ishikawa T, Ullah S, Lee H, Khatri Z, Kim IS (2019) The development of nanofiber tubes based on nanocomposites of polyvinylpyrrolidone incorporated gold nanoparticles as scaffolds for neuroscience application in axons. Text Res J 89(13):2713–2720. https://doi.org/10.1177/0040517518801185
Kenry LCT (2017) Beyond the current state of the syntheses and applications of nanofiber technology. Prog Polym Sci 70:1–17. https://doi.org/10.1016/j.progpolymsci.2017.03.002
Niece KL, Hartgerink JD, Donners JJ, Stupp SI (2003) Self-assembly combining two bioactive peptide-amphiphile molecules into nanofibers by electrostatic attraction. J Am Chem Soc 125(24):7146–7147. https://doi.org/10.1021/ja028215r
Xing X, Wang Y, Li B (2008) Nanofiber drawing and nanodevice assembly in poly (trimethylene terephthalate). Opt Express 16(14):10815–10822. https://doi.org/10.1364/OE.16.010815
Sawicka K, Gouma P, Simon S (2005) Electrospun biocomposite nanofibers for urea biosensing. Sensor Actuators B-Chem 108(1–2):585–588. https://doi.org/10.1016/j.snb.2004.12.013
Eatemadi A, Daraee H, Zarghami N, Melat Yar H, Akbarzadeh A (2016) Nanofiber: synthesis and biomedical applications. Artif Cell Nanomed B 44(1):111–121. https://doi.org/10.3109/21691401.2014.922568
Rahmati M, Mills DK, Urbanska AM, Saeb M, Venugopal JR, Ramakrishna S, Mozafari M (2020) Electrospinning for tissue engineering applications. Prog Mater Sci 100721. https://doi.org/10.1016/j.pmatsci.2020.100721
Bogue R (2009) Nanosensors: a review of recent research. Sens Rev 29(4):310–315. https://doi.org/10.1108/02602280910986539
Srivastava AK, Dev A, Karmakar S (2018) Nanosensors and nanobiosensors in food and agriculture. Environ Chem Lett 16(1):161–182. https://doi.org/10.1007/s10311-017-0674-7
Li C, Chou TW (2006) Atomistic modeling of carbon nanotube-based mechanical sensors. J Intell Material Syst Struct 17(3):247–254. https://doi.org/10.1177/1045389X06058622
Huang Y, Ding M, Guo T, Hu D, Cao Y, Jin L, Guan BO (2017) A fiber-optic sensor for neurotransmitters with ultralow concentration: near-infrared plasmonic electromagnetic field enhancement using raspberry-like meso-SiO2 nanospheres. Nanoscale 9(39):14929–14936. https://doi.org/10.1039/C7NR05032A
Rong G, Tuttle EE, Reilly AN, Clark HA (2019) Recent developments in nanosensors for imaging applications in biological systems. Annu Rev Anal Chem 12:109–128. https://doi.org/10.1146/annurev-anchem-061417-125747
Nascimento RA, Özel RE, Mak WH, Mulato M, Singaram B, Pourmand N (2016) Single cell “glucose nanosensor” verifies elevated glucose levels in individual cancer cells. Nano lett 16:1194–1200. https://doi.org/10.1021/acs.nanolett.5b04495
Khongkow M, Yata T, Boonrungsiman S, Ruktanonchai UR, Graham D, Namdee K (2019) Surface modification of gold nanoparticles with neuron-targeted exosome for enhanced blood–brain barrier penetration. Sci Rep 9(1):1–9. https://doi.org/10.1038/s41598-019-44569-6
Vilella A, Belletti D, Sauer AK, Hagmeyer S, Sarowar T, Masoni M, Grabrucker AM (2018) Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer’s disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery. J Trace Elem Med Biol 49:210–221. https://doi.org/10.1016/j.jtemb.2017.12.006
Aguilera G, Berry CC, West RM, Gonzalez-Monterrubio E, Angulo-Molina A, Arias-Carrión Ó, Méndez-Rojas MÁ (2019) Carboxymethyl cellulose coated magnetic nanoparticles transport across a human lung microvascular endothelial cell model of the blood–brain barrier. Nanoscale Adv 1(2):671–685. https://doi.org/10.1039/C8NA00010G
Cheng Y, Dai Q, Morshed RA, Fan X, Michelle L, Wegscheid ML et al (2014) Blood-brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging. Small (24):5137–5150. https://doi.org/10.1002/smll.201400654
Dong J, Wang K, Sun L, Sun B, Yang M, Chen H, Dong L (2018) Application of graphene quantum dots for simultaneous fluorescence imaging and tumor-targeted drug delivery. Sens Actuators B: Chem 256:616–623. https://doi.org/10.1016/j.snb.2017.09.200
Imamura Y, Yamada S, Tsuboi S, Nakane Y, Tsukasaki Y, Komatsuzaki A, Jin T (2016) Near-infrared emitting PbS quantum dots for in vivo fluorescence imaging of the thrombotic state in septic mouse brain. Molecules 21(8):1080. https://doi.org/10.3390/molecules21081080
Guo X, Lie Q, Liu Y, Jia Z, Gong Y, Yuan X, Liu J (2021) Multifunctional selenium quantum dots for the treatment of Alzheimer’s disease by reducing Aβ-neurotoxicity and oxidative stress and alleviate neuroinflammation. ACS Appl Mater Interfaces 13(26):30261–30273. https://doi.org/10.1021/acsami.1c00690
Campbell E, Hasan MT, Gonzalez Rodriguez R, Akkaraju GR, Naumov AV (2019) Doped graphene quantum dots for intracellular multicolor imaging and cancer detection. ACS Biomater Sci Eng 5(9):4671–4682. https://doi.org/10.1021/acsbiomaterials.9b00603
Garrudo FF, Chapman CA, Hoffman PR, Udangawa RW, Silva JC, Mikael PE, Linhardt RJ (2019) Polyaniline-polycaprolactone blended nanofibers for neural cell culture. Eur Polym J 117:28–37. https://doi.org/10.1016/j.eurpolymj.2019.04.048
Wang DP, Jin KY, Zhao P, Lin Q, Kang K, Hai J (2021) Neuroprotective effects of VEGF-A nanofiber membrane and FAAH inhibitor URB597 against oxygen–glucose deprivation-induced ischemic neuronal injury. Int J Nanomedicine 16:3661. https://doi.org/10.2147/IJN.S307335
Steffens L, Morás AM, Arantes PR, Masterson K, Cao Z, Nugent M, Moura DJ (2020) Electrospun PVA-dacarbazine nanofibers as a novel nano brain-implant for treatment of glioblastoma: in silico and in vitro characterization. Eur J Pharm Sci 143:105183. https://doi.org/10.1016/j.ejps.2019.105183
Nakielski P, Kowalczyk T, Zembrzycki K, Kowalewski TA (2015) Experimental and numerical evaluation of drug release from nanofiber mats to brain tissue. J Biomed Mater Res B Appl Biomater 103 (2): 282–291. https://doi.org/10.1002/jbm.b.33197
Yan L, Zhao B, Liu X, Li X, Zeng C, Shi H, Xu X, Lin T, Dai L, Liu Y (2016) Aligned nanofibers from polypyrrole/graphene as electrodes for regeneration of optic nerve via electrical stimulation. ACS Appl Mater Interfaces 8:6834–6840. https://doi.org/10.1021/acsami.5b12843
Wu X, He L, Li W, Li H, Wong WM, Ramakrishna S, Wu W (2017) Functional self-assembling peptide nanofiber hydrogel for peripheral nerve regeneration. Regen Biomater 4(1):21–30. https://doi.org/10.1093/rb/rbw034
Koutsopoulos S (2016) Self-assembling peptide nanofiber hydrogels in tissue engineering and regenerative medicine: progress, design guidelines, and applications. J Biomed Mater Res B 104(4):1002–1016. https://doi.org/10.1002/jbm.a.35638
Nune M, Subramanian A, Krishnan UM, Sethuraman S (2019) Peptide nanostructures on nanofibers for peripheral nerve regeneration. J Tissue Eng Regen Med 13(6):1059–1070. https://doi.org/10.1002/term.2860
Feng ZQ, Wang T, Zhao B, Li J, Jin L (2015) Soft graphene nanofibers designed for the acceleration of nerve growth and development. Adv Mater 27:6462–6468. https://doi.org/10.1002/adma.201503319
Guo Y, Jiang S, Grena BJ, Kimbrough IF, Thompson EG, Fink Y, Sontheimer H, Yoshinobu T, Jia X (2017) Polymer composite with carbon nanofibers aligned during thermal drawing as a microelectrode for chronic neural interfaces. ACS Nano 11(7):6574–6658. https://doi.org/10.1021/acsnano.6b07550
Yang G, Kampstra KL, Abidian MR (2014) High performance conducting polymer nanofiber biosensors for detection of biomolecules. Adv Mater 26(29):4954–4960. https://doi.org/10.1002/adma.201400753
Rong G, Kim EH, Qiang Y, Di W, Zhong Y, Zhao X, Fang H, Clark HA (2018) Imaging sodium flux during action potentials in neurons with fluorescenanont nanosensors and transparent microelectrodes. ACS sensors 3(12):2499–2505. https://doi.org/10.1021/acssensors.8b00903
Ansari AQ, Ansari SJ, Khan MQ, Khan MF, Qureshi UA, Khatri Z, Ahmad F, Kim IS (2019) Electrospun Zein nanofibers as drug carriers for controlled delivery of Levodopa in Parkinson syndrome. Mater Res Express 6(7):075405. https://doi.org/10.1088/2053-1591/ab16bf
Wang J, Tian L, He L, Chen N, Ramakrishna S, So KF, Mo X (2018) Lycium barbarum polysaccharide encapsulated poly lactic-co-glycolic acid Nanofibers: cost effective herbal medicine for potential application in peripheral nerve tissue engineering. Sci Rep 8(1):8669. https://doi.org/10.1038/s41598-018-26837-z
Nguyen LH, Gao M, Lin J, Wu W, Wang J, Chew SY (2017) Three-dimensional aligned nanofibers-hydrogel scaffold for controlled non-viral drug/gene delivery to direct axon regeneration in spinal cord injury treatment. Sci Rep 7:42212. https://doi.org/10.1038/srep42212
Hembury M, Chiappini C, Bertazzo S et al (2015) Gold–silica quantum rattles for multimodal imaging and therapy. PNAS 112:1959–1964. https://doi.org/10.1073/pnas.1419622112
Luo Y, Kim EH, Flask CA, Clark HA (2018) Nanosensors for the chemical imaging of acetylcholine using magnetic resonance imaging. ACS Nano 12(6):5761–5773. https://doi.org/10.1021/acsnano.8b01640
Layton KN, Abidian MR (2011) Conducting polymer nanofiber-based biosensor for detection of neurochemicals. 2011 5th International IEEE/EMBS Conference on Neural Engineering: 298–301. https://doi.org/10.1109/NER.2011.5910546
Shi Y, Pan Y, Zhang H, Zhang Z, Li MJ, Yi C, Yang M (2014) A dual-mode nanosensor based on carbon quantum dots and gold nanoparticles for discriminative detection of glutathione in human plasma. Biosens Bioelectron 56:39–45. https://doi.org/10.1016/j.bios.2013.12.038
Kruss S, Salem DP, Vuković L, Lima B, Vander Ende E, Boyden ES, Strano MS (2017) High-resolution imaging of cellular dopamine efflux using a fluorescent nanosensor array. Proc Natl Acad Sci USA 114:1789–1794. https://doi.org/10.1073/pnas.1613541114
Zhou X, Ma P, Wang A, Yu C, Qian T, Wu S, Shen J (2015) Dopamine fluorescent sensors based on polypyrrole/graphene quantum dots core/shell hybrids. Biosens Bioelectron 64:404–410. https://doi.org/10.1016/j.bios.2014.09.038
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
(Corresponding author: M. Mozafari, PhD; Currently at: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.)
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Batool, S., Nabipour, H., Ramakrishna, S. et al. Nanotechnology and quantum science enabled advances in neurological medical applications: diagnostics and treatments. Med Biol Eng Comput 60, 3341–3356 (2022). https://doi.org/10.1007/s11517-022-02664-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11517-022-02664-3