Abstract
The latest progress of using carbon nanotubes (CNTs) for in vivo cancer nanotechnology is reviewed. CNTs can be functionalized by either covalent or non-covalent chemistry to produce functional bioconjugates for many in vivo applications. In vivo behaviors and toxicology studies of CNTs are summarized, suggesting no significant toxicity of well functionalized CNTs to the treated mice. Owing to their unique chemical and physical properties, CNTs, especially single-walled carbon nanotubes (SWNTs), have been widely used for various modalities of in vivo cancer treatment and imaging. Future development of CNT-based nanomedicine may bring novel opportunities to cancer diagnosis and therapy.
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References
Iijima S. Helical microtubules of graphitic carbon. Nature, 1991, 354: 56–58
Liu Z, Tabakman S, Welsher K, Dai H. Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery. Nano Res, 2009, 2(2): 85–120
Kostarelos K, Bianco A, Prato M. Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat Nanotechnol, 2009, 4: 627–633
Liu Z, Tabakman SM, Chen Z, Dai H. Preparation of carbon nanotube bioconjugates for biomedical applications. Nat Protoc, 2009, 4: 1372–1382
Liu Z, Sun X, Nakayama N, Dai H. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano, 2007, 1(1): 50–56
Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H. Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res, 2008, 68: 6652–6660
Prencipe G, Tabakman SM, Welsher K, Liu Z, Goodwin AP, Zhang L, Henry J, Dai HJ. PEG Branched polymer for functionalization of nanomaterials with ultralong blood circulation. J Am Chem Soc, 2009, 131(13): 4783–4787
McDevitt MR, Chattopadhyay D, Kappel BJ, Jaggi JS, Schiffman SR, Antczak C, Njardarson JT, Brentjens R, Scheinberg DA. Tumor targeting with antibody-functionalized, radiolabeled carbon nanotubes. J Nucl Med, 2007, 48(7): 1180–1189
Ali-Boucetta H, Al-Jamal KT, McCarthy D, Prato M, Bianco A, Kostarelos K. Multiwalled carbon nanotube-doxorubicin supramolecular complexes for cancer therapeutics. Chem Commun, 2008, (4): 459–461
Kam NWS, O’Connell M, Wisdom JA, Dai H. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci, 2005, 102(33): 11600–11605
Moon HK, Lee SH, Choi HC. In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. ACS Nano, 2009, 3(11): 3707–3713
Zerda Adl, Zavaleta C, Keren S, Vaithilingam S, Bodapati S, Liu Z, Levi J, Ma T-J, Oralkan O, Cheng Z, Chen X, Dai H, Khuri-Yakub BP, Gambhir SS. Photoacoustic molecular imaging in living mice utilizing targeted carbon nanotubes. Nat Nanotechnol, 2008, 3: 557–562
Chakravarty P, Marches R, Zimmerman NS, Swafford ADE, Bajaj P, Musselman IH, Pantano P, Draper RK, Vitetta ES. Thermal ablation of tumor cells with anti body-functionalized single-walled carbon nanotubes. Proc Natl Acad Sci, 2008, 105(25): 8697–8702
Cherukuri P, Bachilo SM, Litovsky SH, Weisman RB. Near-infrared fluorescence microscopy of single-walled carbon nanotubes in phagocytic cells. J Am Chem Soc, 2004, 126(48): 15638–15639
Cherukuri P, Gannon CJ, Leeuw TK, Schmidt HK, Smalley RE, Curley SA, Weisman RB. Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc Natl Acad Sci, 2006, 103(50): 18882–18886
Welsher K, Liu Z, Sherlock SP, Robinson JT, Chen Z, Daranciang D, Dai H. A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nat Nanotechnol, 2009, 4: 773–780
Welsher K, Liu Z, D D, Dai H. Selective probing and imaging of cells with single walled carbon nanotubes as near-infrared fluorescent molecules. Nano Lett, 2008, 8(2): 586–590
Jin H, Heller DA, Strano MS. Single-particle tracking of endocytosis and exocytosis of single-walled carbon nanotubes in NIH-3T3 cells. Nano Lett, 2008, 8(6): 1577–1585
Liu Z, Tabakman S, Sherlock S, Li X, Chen Z, Jiang K, Fan S, Dai H. Multiplexed five-color molecular imaging of cancer cells and tumor tissues with carbon nanotube Raman tags in the near-infrared. Nano Res, 2010, 3(3): 222–223
Liu Z, Li X, Tabakman SM, Jiang K, Fan S, Dai H. Multiplexed multi-color Raman imaging of live cells with isotopically modified single walled carbon nanotubes. J Am Chem Soc, 2008, 130: 13540–13541
Liu Z, Davis C, Cai W, He L, Chen X, Dai H. Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc Natl Acad Sci, 2008, 105(5): 1410–1415
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, 2005, 17(23): 2793–2799
Hirsch A, Vostrowsky O. Functionalization of carbon nanotubes. Top Curr Chem, 2005, 245: 193–237
Nie H, Guo W, Yuan Y, Dou Z, Shi Z, Liu Z, Wang H, Liu Y. PE-Gylation of double-walled carbon nanotubes for increasing their solubility in water. Nano Res, 2010, 3(2): 103–109
Tagmatarchis N, Prato M. Functionalization of carbon nanotubes via 1,3-dipolar cycloadditions. J Mater Chem, 2004, 14(4): 437–439
Moon HK, Chang CI, Lee D-K, Choi HC. Effect of nucleases on the cellular internalization of fluorescent labeled DNA-functionalized single-walled carbon nanotubes. Nano Res, 2008, 1(4): 351–360
Sayes CM, Liang F, Hudson JL, Mendez J, Guo WH, Beach JM, Moore VC, Doyle CD, West JL, Billups WE, Ausman KD, Colvin VL. Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett, 2006, 161(2): 135–142
Liu Z, Fan A, Rakhra K, Sherlock S, Goodwin A, Chen X, Yang Q, Felsher D, Dai H. Supramolecular stacking of doxorubicin on carbon nanotubes for in vivo cancer therapy. Angew Chem Int Ed, 2009, 48: 7668–7672
Liu Z, Cai WB, He LN, Nakayama N, Chen K, Sun XM, Chen XY, Dai HJ. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat Nanotechnol, 2007, 2(1): 47–52
Liu Z, Winters M, Holodniy M, Dai HJ. siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem Int Ed, 2007, 46(12): 2023–2027
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): 12492–12493
Wang HF, Wang J, Deng XY, Sun HF, Shi ZJ, Gu ZN, Liu YF, Zhao YL. Biodistribution of carbon single-wall carbon nanotubes in mice. J Nanosci Nanotechnol, 2004, 4(8): 1019–1024
Deng X, Jia G, Wang H, Sun H, Wang X, Yang S, Wang T, Liu Y. Translocation and fate of multi-walled carbon nanotubes in vivo. Carbon, 2007, 45(7): 1419–1424
Deng XY, Yang ST, Nie HY, Wang HF, Liu YF. A generally adoptable radiotracing method for tracking carbon nanotubes in animals. Nanotechnology, 2008, 19(7): 075101
Singh R, Pantarotto D, Lacerda L, Pastorin G, Klumpp C, Prato M, Bianco A, Kostarelos K. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc Nat Acad Sci, 2006, 103(9): 3357–3362
Lacerda L, Soundararajan A, Singh R, Pastorin G, Al-Jamal KT, Turton J, Frederik P, Herrero MA, Bao SLA, Emfietzoglou D, Mather S, Phillips WT, Prato M, Bianco A, Goins B, Kostarelos K. Dynamic Imaging of functionalized multi-walled carbon nanotube systemic circulation and urinary excretion. Adv Mater, 2008, 20(2): 225–230
Lam CW, James JT, McCluskey R, Hunter RL. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Lett, 2004, 77(1): 126–134
Warheit DB, Laurence BR, Reed KL, Roach DH, Reynolds GAM, Webb TR. Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Lett, 2004, 77(1): 117–125
Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH, Seaton A, Stone V, Brown S, MacNee W, Donaldson K. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol, 2008, 3: 423–428
Schipper ML, Nakayama-Ratchford N, Davis CR, Kam NWS, Chu P, Liu Z, Sun X, Dai H, Gambhir SS. A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. Nat Nanotechnol, 2008, 3(4): 216–221
Yang ST, Wang X, Jia G, Gu Y, Wang T, Nie H, Ge C, Wang H, Liu Y. Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice. Toxicol Lett, 2008, 181(3): 182–189
Kolosnjaj-Tabi J, Hartman KB, Boudjemaa S, Ananta JS, Morgant G, Szwarc H, Wilson LJ, Moussa F. In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to swiss mice. ACS Nano, 2010, 4(3): 1481–1492
Wu W, Li RT, Bian XC, Zhu ZS, Ding D, Li XL, Jia ZJ, Jiang XQ, Hu YQ. Covalently combining carbon nanotubes with anticancer agent: Preparation and antitumor activity. Acs Nano, 2009, 3(9): 2740–2750
Ghosh S, Dutta S, Gomes E, Carroll D, D’Agostino R, Olson J, Guthold M, Gmeiner WH. Increased heating efficiency and selective thermal ablation of malignant tissue with DNA-encased multiwalled carbon nanotubes. Acs Nano, 2009, 3(9): 2667–2673
Kam NWS, Dai H. Carbon nanotubes as intracellular protein transporters: Generality and biological functionality. J Am Chem Soc, 2005, 127(16): 6021–6026
Kam NWS, Liu ZA, Dai HJ Carbon nanotubes as intracellular transporters for proteins and DNA: An investigation of the uptake mechanism and pathway. Angew Chem Int Ed, 2006, 45(4): 577–581.
Kostarelos K, Lacerda L, Pastorin G, Wu W, Wieckowski S, Luangsivilay J, Godefroy S, Pantarotto D, Briand JP, Muller S, Prato M, Bianco A. Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type. Nat Nanotechnol, 2007, 2(2): 108–113
Kam NWS, Jessop TC, Wender PA, Dai HJ. Nanotube molecular transporters: Internalization of carbon nanotube-protein conjugates into mammalian cells. J Am Chem Soc, 2004, 126(22): 6850–6851
Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov, 2006, 5(3): 219–234
Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Contr Rel, 2000, 65(1–2): 271–284
Sun X, Liu Z, Welsher K, Robinson JT, Goodwin A, Zaric S, Dai H. Nano-graphene oxide for cellular imaging and drug delivery. Nano Res, 2008, 1(3): 203–212
Liu Z, Robinson JT, Sun XM, Dai HJ. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc, 2008, 130(33): 10876–10877
Dhar S, Liu Z, Thomale J, Dai H, Lippard SJ. Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device. J Am Chem Soc, 2008, 130: 11467–11476
Pantarotto D, Singh R, McCarthy D, Erhardt M, Briand JP, Prato M, Kostarelos K, Bianco A. Functionalized carbon nanotubes for plasmid DNA gene delivery. Angew Chem Int Ed, 2004, 43(39): 5242–5246
Singh R, Pantarotto D, McCarthy D, Chaloin O, Hoebeke J, Partidos CD, Briand JP, Prato M, Bianco A, Kostarelos K. Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: Toward the construction of nanotube-based gene delivery vectors. J Am Chem Soc, 2005, 127(12): 4388–4396
Gao LZ, Nie L, Wang TH, Qin YJ, Guo ZX, Yang DL, Yan XY. Carbon nanotube delivery of the GFP gene into mammalian cells. Chembiochem, 2006, 7(2): 239–242
Liu Y, Wu DC, Zhang WD, Jiang X, He CB, Chung TS, Goh SH, Leong KW. Polyethylenimine-grafted multiwalled carbon nanotubes for secure noncovalent immobilization and efficient delivery of DNA. Angew Chem Int Ed, 2005, 44(30): 4782–4785
Mello CC, Conte D. Revealing the world of RNA interference. Nature, 2004, 431(7006): 338–342
Zhang ZH, Yang XY, Zhang Y, Zeng B, Wang ZJ, Zhu TH, Roden RBS, Chen YS, Yang RC. Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single-walled carbon nanotubes suppresses tumor growth. Clin Cancer Res, 2006, 12(16): 4933–4939
Bartholomeusz G, Cherukuri P, Kingston J, Cognet L, Lemos R, Leeuw TK, Gumbiner-Russo L, Weisman RB, Powis G. In vivo therapeutic silencing of hypoxia-inducible factor 1 alpha (HIF-1alpha) using single-walled carbon nanotubes noncovalently coated with siRNA. Nano Res, 2009, 2(4): 279–291
Gannon CJ, Cherukuri P, Yakobson BI, Cognet L, Kanzius JS, Kittrell C, Weisman RB, Pasquali M, Schmidt HK, Smalley RE, Curley SA. Carbon nanotube-enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field. Cancer, 2007, 110(12): 2654–2665
Zavaleta C, Zerda Adl, Liu Z, Keren S, Cheng Z, Schipper M, Chen X, Dai H, Gambhir SS. Noninvasive Raman spectroscopy in living mice for evaluation of tumor targeting with carbon nanotubes. Nano Lett, 2008, 8(9): 2800–2805
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Zhang, S., Yang, K. & Liu, Z. Carbon nanotubes for in vivo cancer nanotechnology. Sci. China Chem. 53, 2217–2225 (2010). https://doi.org/10.1007/s11426-010-4115-8
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DOI: https://doi.org/10.1007/s11426-010-4115-8