Functionalized carbon nanotubes—A boon in treating brain diseases

Rajkumar Ghosh Jagabandhu Bag Aparna Datta Arup Pramanick Isa Hassan Abubakar   

Open Access   

Published:  Feb 25, 2023

DOI: 10.7324/JAPS.2023.107158

Typical intrinsic properties of carbon nanotube (CNTs) like one-dimensional structure with very high mechanical strength, high thermal and electrical conductivity, high aspect ratio, high surface area, ability to conjugate with functional groups, and elevated surface functionalizing capacity have made it a nanostructure of choice to be manipulated for drug delivery for the past two decades. The human brain restricts movements and or entry of ions, molecules, and cells between the blood and the brain because of the presence of the blood–brain barrier. As a result, administering drug molecules of choice to the brain under disease condition become constrained. Surface functionalized CNTs can render themselves efficient as drug carriers to the neurons, for extreme conditions like Alzheimer’s disease, glioblastoma, Parkinson’s disorder, brain stroke, brain tumor, etc. This review discussed in detail the advancement achieved so far in delivering drug molecules to the brain using CNT as the carrier and related management of toxicity so that a safer dose delivery can be made.

Keyword:     Carbon nanotube brain-diseases functionalization blood–brain barrier toxicity


Ghosh R, Bag J, Datta A, Pramanick A, Abubakar IH. Functionalized carbon nanotubes—A boon in treating brain diseases. J Appl Pharm Sci, 2023.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Alimohammadi E, Nikzad A, Khedri M, Rezaian M, Jahromi AM, Rezaei N, Maleki R. Potential treatment of Parkinson's disease using new-generation carbon nanotubes: a biomolecular in silico study. Nanomedicine (Lond), 2021; 16(3):189-204.

Al-Jamal KT, Gherardini L, Bardi G, Nunes A, Guo C, Bussy C, Herrero MA, Bianco A, Prato M, Kostarelos K, Pizzorusso T. Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing. Proc Natl Acad Sci, 2011; 108(27):10952-7.

Bardi G, Nunes A, Gherardini L, Bates K, Al-Jamal KT, Gaillard C, Prato M, Bianco A, Pizzorusso T, Kostarelos K. Functionalized carbon nanotubes in the brain: cellular internalization and neuroinflammatory responses. PLoS One, 2013; 8(11):e80964.

Barker RA, TRANSEURO consortium. Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease. Nat Med, 2019; 25(1):1045-53.

Beg S, Rizwan M, Sheikh AM, Hasnain MS, Anwer K, Kohli K. Advancement in carbon nanotubes: basics, biomedical applications and toxicity. J Pharm Pharmacol, 2011; 63(2):141-63.

Ben-Jacob E, HaneinY. Carbon nanotube microelectrodes for neuronal interfacing. J Mater Chem, 2008; 18(43):5181.

Bhattacharya K, Sacchetti C, El-Sayed R, Fornara A, Kotchey GP, Gaugler JA, Star A, Bottini M, Fadeel B. Enzymatic 'stripping' and degradation of PEGylated carbonnanotubes. Nanoscale, 2014; 6(24):14686-90.

Bianco A, Prato M. Can carbon nanotubes be considered useful tools for biological applications? Adv Mater Lett, 2003; 15(1):1765-8.

Bicker J, Alves G, Fortuna A, Falcão A. Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review. Eur J Pharm Biopharm, 2014; 87(3):409-32.

Bjartmarz H, Rehncrona S. Comparison of accuracy and precision between frame-based and frameless stereotactic navigation for deep brain stimulation electrode implantation. Stereotact Funct Neurosurg, 2007; 85(5):235-42.

Caoduro C, Hervouet E, Girard-Thernier C, Gharbi T, Boulahdour H, Delage-Mourroux R, Pudlo M. Carbon nanotubes as gene carriers: focus on internalization pathways related to functionalization and properties. ActaBiomater, 2017; 49(1):36-44.

Chenthamara D, Subramaniam S, Ramakrishnan SG, Krishnaswamy S, Essa MM, Lin FH, Qoronfleh MW. Therapeutic efficacy of nanoparticles and routes of administration. Biomater Res, 2019; 23;20.

Costa PM, Bourgognon M, Wang JT, Al-Jamal KT. Functionalized carbon nanotubes: From intracellular uptake and cell-related toxicity to systemic brain delivery. J Control Release, 2004; 241(1):200-219.

Dawson TM, Golde TE, Lagier-Tourenne C. Animal models of neurodegenerative diseases. Nat Neurosci, 2018; 21(10):1370-9.

Dugan LL, Lovett EG, Quick KL, Lotharius J, Lin TT, O'Malley KL. Fullerene-based antioxidants and neurodegenerative disorders. Parkinson Relat Disord, 2001; 7(1):243-6.

Dugan LL, Turetsky DM, Du C, Lobner D, Wheeler M, Almli CR, Shen CK, Luh TY, Choi DW, Lin TS. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci USA, 1997; 94(1):9434-9.

Dvir T, Timko BP, Kohane DS, Langer R. Nanotechnological strategies for engineering complex tissues. Nat Nanotechnol, 2011; 6(1):13-22.

Fabbro A, Prato M, Ballerini L. Carbon nanotubes in neuroregeneration and repair. Adv Drug Deliv Rev, 2013; 65(1):2034-44.

Fisher C, Rider AE, Han ZJ, Kumar S, Levchenko I, Ostrikov K. Application and nanotoxicity of carbon nanotubes and graphene in biomedicine. J Nanomater, 2012; 2012(1):315185.

Folch J, Petrov D, Ettcheto M, Abad S, Sánchez-López E, García ML, Olloquequi J, Beas-Zarate C, Auladell C, Camins A. Current research therapeutic strategies for Alzheimer's disease treatment. Neural Plasti, 2016; 8501693.

Georgakilas V, Kordatos K, Prato M, Guldi DM, Holzinger M, Hirsch A. Organic functionalization of carbon nanotubes. J Am Chem Soc, 2002; 124(5):760-1.

Guo Q, Shen XT, Li YY, Xu SQ. Carbon nanotubes-based drug delivery to cancer and brain. J Huazhong Univ Sci Technolog Med Sci, 2017; 37(5):635-41.

Harsha P, Thotakura N, Kumar M, Sharma S, Mittal A, Khurana RK, Singh B, Negi P, Raza K. A novel PEGylatedcarbon nanotube conjugated mangiferin: an explorative nanomedicine for brain cancer cells. J Drug DelivSciTechnol, 2019; 53(1):101186.

He P, Dai L. Aligned carbon nanotube-DNA electrochemical sensors. Chemcomm, 2004; 10(3):348-9.

Heller DA, Baik S, Eurell TE, Strano MS. Single walled carbon nanotube spectroscopy in live cells: towards long-term labels and optical sensors. Adv Mater Lett, 2005; 17(23):2793-9.

Heller DA, Jeng ES, Yeung TK, Martinez BM, Moll AE, Gastala JB, Strano MS. Optical detection of DNA conformational polymorphism on single-walled carbon nanotubes. Science, 2006; 311(5760):508-11.

Hong G, Diao S, Chang J, Antaris AL, Chen C, Zhang B, Zhao S, Atochin DN, Huang PL, Andreasson KI, Kuo CJ, Dai H. Through-skull fluorescence imaging of the brain in a new near-infrared window. Nat Photonics, 2014; 8(9):723-30.

Iijima S. Helical microtubules of graphitic carbon. Nature, 1991; 354(1):56-8.

Iverson NM, Barone PW, Shandell M, Trudel LJ, Sen S, Sen F, Ivanov V, Atolia E, Farias E, McNicholas TP, Reuel N, Parry NMA, Wogan GN, Strano MS. In vivo biosensing via tissue-localizable near-infrared-fluorescent single walled carbon nanotubes. Nat Nanotechnol, 2013; 8(11):873-80.

Jacobs CB, Ivanov IN, Nguyen MD, Zestos AG, Venton BJ. High temporal resolution measurements of dopamine with carbon nanotube yarn microelectrodes. Anal Chem, 2014; 86(12):5721-7.

Jeong Y, Lee HJ, Lee DY, Noh YH, Do Hee KI, Kim OH, Park JA, Jiwon LE, inventors. BRAINGUARD CO Ltd. Use of carbon nanotubes for preventing or treating brain disease. European Patent EP2594289A4. 2011-07-14.

Ji S, Liu C, Zhang B, Yang F, Xu J, Long J, Jin C, Fu D, Ni Q, Yu X. Carbon nanotubes in cancer diagnosis and therapy. Biochim Biophys Acta Rev Cancer, 2010; 1806(1):29-35.

John AA, Subramanian AP, Vellayappan MV, A. Balaji, Mohandas H, Jaganathan SK. Carbon nanotubes and graphene as emerging candidates in neuroregeneration and neurodrug delivery. Int J Nanomedicine, 2015; 10(312):4267-77.

Kafa H, Wang JT, Rubio N, Klippstein R, Costa PM, Hassan HA, Sosabowski JK, Bansal SS, Preston JE, Abbott NJ, Al-Jamal KT. Translocation of LRP1 targeted carbon nanotubes of different diameters across the blood-brain barrier in vitro and in vivo. J Control Release, 2016; 225(1):217-29.

Kagan VE, Konduru NV, Feng W, Allen BL, Conroy J, Volkov Y, Vlasova II, Belikova NA, Yanamala N, Kapralov A, Tyurina YY, Shi J, Kisin ER, Murray AR, Franks J, Stolz D, Gou P, Klein-Seetharaman J, Fadeel B, Star A, Shvedova AA. Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nat Nanotechnol, 2010; 5(5):354-9.

Kakkar AK, Dahiya N. Management of Parkinson's disease: current and future pharmacotherapy. Eur J Pharmacol, 2015; 750(1):74-81.

Kam NWS, Liu Z, Dai H. Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. J Am Chem Soc, 2005; 127(36):12492-3.

Kaur S, Mehra NK, Jain K, Jain NK. Development and evaluation of targeting ligand-anchored CNTs as prospective targeted drug delivery system. Artif Cells Nanomed Biotechnol, 2017; 45(2):242-50.

Kerna NA, Flores JV, Pruitt KD, Nwokorie U, Holets H. The application of fullerene derivatives in human nutrition: brain health, immunity, longevity, quality of life, skin tone, sports performance, vitality, and weight Loss. EC Nutrition, 2020; 15(1):01-06.

Khuloud A. Carbon nanotubes deliver in medicine Am Sci, 2015; 103(1):122-8.

Kim K, Kim MJ, Kim DW, Kim SY, Park S, Park CB. Clinically accurate diagnosis of Alzheimer's disease via multiplexed sensing of core biomarkers in human plasma. Nat Commun, 2020; 11(1):119.

Komane PP, Choonara YE, du Toit LC, Kumar P, Kondiah PDP, Modi G, Pillay V. Diagnosis and treatment of neurological and ischemic disorders employing carbon nanotube technology. J Nanomat, 2016; 9417874:19.

Kostarelos K, Bianco A, Prato M. Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat Nanotechnol, 2009; 4(10):627-33.

Kumar LA, Pattnaik G, Satapathy BS, Swapna S, Mohanty D. Targeting to brain tumor: nanocarrier-based drug delivery platforms, opportunities, and challenges. J Pharm Bioallied Sci, 2021; 13(2):172-7.

Lee HJ, Park J, Yoon OJ, Kim HW, Lee DY, Kim DH, Lee WB, Lee NE, Bonventre JV, Kim SS. Amine-modified single-walled carbon nanotubes protect neurons from injury in a rat stroke model. Nat Nanotechnol, 2011; 6(2):121-5.

Lee SJ, Zhu W, Nowicki M, Lee G, Heo DN, Kim J, Zuo Y, Zhang LG. 3D printing nano conductive multi-walled carbon nanotube scaffolds for nerve regeneration. J Neural Eng, 2018; 15(1):016018.

Li S, Gu X, Yi S. The regulatory effects of transforming growth factor-β on nerve regeneration. Cell Transplant, 2017; 26(1):381-94. Li Z, de Barros ALB, Soares DCF, Moss SN, Alisaraie L. Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery. Int J Pharm, 2017; 524(1-2):41-54.

Lin CM, Lee YT, Yeh SR, Fang W. Flexible carbon nanotubes electrode for neural recording. Biosens Bioelectron, 2009; 24(9):2791-7.

Liu Y, Zhao Y, Sun B, Chen C. Understanding the toxicity of carbon nanotubes. Acc Chem Res, 2013; 46(3):702-13.

Malarkey EB, Parpura V. Applications of carbon nanotubes in neurobiology. Neurodegener Dis, 2007; 4(1):292-9.

Markovic ZM, Harhaji-Trajkovic LM, Todorovic- Markovic BM, Kepi? DP, Arsikin KM, Jovanovi? SP, Pantovic AC, Drami?anin MD, Trajkovic VS. In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. Biomaterials, 2011; 32(4):1121-9.

Martincic M, Tobias G. Filled carbon nanotubes in biomedical imaging and drug delivery. Expert Opin Drug Deliv, 2015; 12(4):563-81.

Mattson MP, Haddon RC, Rao AM. Molecular functionalization of carbon nanotubes and use as substrates for neuronal growth. J Mol Neurosci, 2000; 14(3):175-82.

More SV, Choi DK. Promising cannabinoid-based therapies for Parkinson's disease: motor symptoms to neuroprotection. Mol Neurodegener, 2015; 10(17):1-26.

Nunes A, Al-Jamal K, Nakajima T, Hariz M, Kostarelos K. Application of carbon nanotubes in neurology: clinical perspectives and toxicological risks. Arch Toxicol, 2012; 86(7):1009-20.

Nunes A, Al-Jamal KT, Kostarelos K. Therapeutics, imaging and toxicity of nanomaterials in the central nervous system. J Control Release, 2012; 161(2):290-306.

Pardridge WM. Blood-brain barrier and delivery of protein and gene therapeutics to brain. Front Aging Neurosci, 2020; 11(373):1-27.

Pantarotto D, Briand JP, Prato M, Bianco A. Translocation of bioactive peptides across cell membranes by carbon nanotubes. Chem Commun (Camb), 2004; 1(1):16-7.

Place ES, Evans ND, Stevens MM. Complexity in biomaterials for tissue engineering. Nat Mater, 2009; 8(1):457-70.

Podolski IY, Podlubnaya ZA, Kosenko EA, Mugantseva EA, Makarova EG, Marsagishvili LG, Shpagina MD, Kaminsky YG, Andrievsky GV, Klochkov VK. Effects of hydrated forms of C60 fullerene on amyloid 1-peptide fibrillization in vitro and performance of the cognitive task. J NanosciNanotechnol, 2007; 7(4-5):1479-85.

Ren J, Shen S, Wang D, Xi Z, Guo L, Pang Z, Qian Y, Sun X, Jiang X. The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials, 2012; 33(11):3324-33.

Santos T, Fang X, Chen MT, Wang W, Ferreira R, Jhaveri N, Gundersen M, Zhou C, Pagnini P, Hofman FM, Chen TC. Sequential administration of carbonnanotubes and near-infrared radiation for the treatment of gliomas. Front Oncol, 2014; 4(1):180.

Sharma HS, Muresanu DF, Sharma A. Novel therapeutic strategies using nanodrug delivery, stem cells and combination therapy for CNS trauma and neurodegenerative disorders. Expert Rev Neurother, 2013; 13(10):1085-8.

Soligo M, Felsani FM, Ros TD, Bosi S, Pellizzoni E, Bruni S, Isopi J, Marcaccio M, Mannia L, Fiorito S. Distribution in the brain and possible neuroprotective effects of intranasally delivered multi-walled carbon nanotubes. Nanoscale Adv, 2021; 3(1):418-31.

Stephenson J, Nutma E, van der Valk P, Amor S. Inflammation in CNS neurodegenerative diseases. Immunology, 2018;154(2):204-19.

Tan J, Wang Y, Yip X, Glynn F, Shepherd RK, Caruso F. Nanoporous peptide particles for encapsulating and releasing neurotrophic factors in an animal model of neurodegeneration. Adv Mater, 2012; 24(25):3362-6.

Tan JM, Foo JB, Fakurazi S, Hussein MZ. Release behaviour and toxicity evaluation of levodopa from carboxylated single-walled carbon nanotubes. Beilstein J Nanotechnol, 2015; 6(1):243-53.

Tykhomyrov AA, Nedzvetsky VS, Klochkov VK, Andrievsky GV. Nanostructures of hydrated C60 fullerene (C60HyFn) protect rat brain against alcohol impact and attenuate behavioral impairments of alcoholized animals. Toxicology, 2008; 246(1):158-65.

Vidu R, Rahman M, Mahmoudi M, Enachescu M, Poteca TD, Opris I, Nanostructures: a platform for brain repair and augmentation. Front Syst Neurosci, 2014; 8(91)1-24.

Vorobyov V, Kaptsov V, Gordon R, Makarova E., Podolski I, Sengpiel F. Neuroprotective effects of hydrated fullerene C60: cortical and hippocampal EEG interplay in an amyloid-infused rat model of Alzheimer's disease. J Alzheimer's Dis, 2015; 45(1):217-33.

Wang W, Zhu Y, Liao S, Li J. Carbon nanotubes reinforced composites for biomedical applications. Biomed Res Int, 2014; 2014(1):1-15.

Xiang C, Zhang Y, Guo W, Liang XJ. Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication. Acta Pharm Sin B, 2020; 10(2):239-48.

Xue X, Wang LR, Sato Y, Jiang Y, Berg M, Yang DS, Nixon RA, Liang XJ. Single-walled carbon nanotubes alleviate autophagic/lysosomal defects in primary glia from a mouse model of Alzheimer's disease. Nano Lett, 2014; 14(9):5110-7.

Yang T, Wu Z, Wang P, Mu T, Qin H, Zhu Z, Wang J, Sui L. A large-inner-diameter multi-walled carbon nanotube-based dual-drug delivery system with pH-sensitive release properties. J Mater Sci Mater Med, 2017; 28(7):110.

Yang Z, Zhang Y, Yang Y, Sun L, Han D, Li H, Wang C. Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomed J, 2010; 6(3):427-41.

Zhang L, Liu F, Sun X, Wei G, Tian Y, Liu Z, Huang R, Yu Y, Peng H. Engineering carbon nanotube fiber for real-time quantification of ascorbic acid levels in a live rat model of Alzheimer's disease. Anal Chem, 2017; 89(3):1831-7.

Zhao D, Alizadeh D, Zhang L, Liu W, Farrukh O, Manuel E, Diamond DJ, Badie B. Carbon nanotubes enhance CpG uptake and potentiate antiglioma immunity. Clin Cancer Res, 2011; 17(4):771-82.

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