Nanodiamonds as vehicles for systemic and localized drug delivery

Expert Opinion on Drug Delivery

Volumn 6, Issue 9, 2009, Pages 883-895

  Lam, Robert ^a   Ho, Dean ^a,b  

^a Northwestern University   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Cancer; Drug delivery; Imaging; Nanodiamond; Targeting

Indexed keywords

DEXAMETHASONE; DOXORUBICIN; NANODIAMOND; NANOMATERIAL; POLYACRYLONITRILE; POLYAMIDE; UNCLASSIFIED DRUG;

BIOCOMPATIBILITY; CANCER THERAPY; CELL MIGRATION; COMPLEX FORMATION; DRUG COATING; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG RELEASE; DRUG UPTAKE; IMPLANT; MICROFILM; MOLECULAR INTERACTION; REVIEW;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOCOMPATIBLE MATERIALS; DIAMOND; DRUG DELIVERY SYSTEMS; HUMANS; NANOSTRUCTURES; NEOPLASMS; SURFACE PROPERTIES;

EID: 70249106102     PISSN: 17425247     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425240903156382     Document Type: Review

References (119)

1. Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano 2009;3(1):16-20
2. Salata OV. Applications of nanoparticles in biology and medicine. J Nanobiotechnol 2004;2(1):3
3. Bakken EE, Heruth K. Temporal control of drugs. Ann NY Acad Sci 1991;618(temporal control of drug delivery):422-427
4. Langer R. New methods of drug delivery. Science 1990;249(4976):1527-1533 • This report discusses important routes towards optimizing nanomaterial-based drug delivery.
5. Yuan F, Dellian M, Fukumura D, et al. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res 1995;55(17):3752-3756
6. Hobbs SK, Monsky WL, Yuan F, et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA 1998;95(8):4607-4612 (Pubitemid 28207960)
7. Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 2002;54(5):631-651
8. Danilenko V. On the history of the discovery of nanodiamond synthesis. Phys Solid State 2004;46(4):595-599
9. Dolmatov VY. Detonation synthesis ultradispersed diamonds: properties and applications. Usp Khim 2001;70(7):687-708
10. Huang HJ, Dai LM, Wang DH, et al. Large-scale self-assembly of dispersed nanodiamonds. J Mater Chem 2008;18(12):1347-1352
11. Osawa E. Recent progress and perspectives in single-digit nanodiamond. Diamond Relat Mater 2007;16(12):2018-2022 (Pubitemid 350117441)
12. Osawa E. Disintegration and purification of crude aggregates of detonation nanodiamond. Synth Properties Appl Ultrananocrystalline Diamond 2005;192:231-240 •• This paper describes the processing of detonation nanodiamonds from aggregate to single particle form, providing an important foundation towards enhancing the biomedical relevance of nanodiamonds with respects to functionalization with bioactive compounds and biocompatibility.
13. Krueger A. The structure and reactivity of nanoscale diamond. J Mater Chem 2008;18(13):1485-1492
14. Lian T, Ho RJY. Trends and developments in liposome drug delivery systems. J Pharm Sci 2001;90(6):667-680 (Pubitemid 32530443)
15. Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev 2001;47(1):113-131 (Pubitemid 32209236)
16. Drummond DC, Meyer O, Hong KL, et al. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 1999;51(4):691-743
17. Hanson JA, Chang CB, Graves SM, et al. Nanoscale double emulsions stabilized by single-component block copolypeptides. Nature 2008;455(7209):85-88 •• Double nanoemulsions synthesized in this work demonstrated unprecedented long-term stability and the capacity for simultaneous loading with hydrophilic and hydrophobic compounds.
18. Paciotti GF, Kingston DGI, Tamarkin L. Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor-targeted drug delivery vectors. Drug Dev Res 2006;67(1):47-54 (Pubitemid 43765048)
19. Rosi NL, Giljohann DA, Thaxton CS, et al. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 2006;312(5776):1027- 1030 •• This work demonstrates the application of gold nanoparticles as RNA delivery agents with preserved intracellular capacity for gene regulation.
20. Lacerda L, Bianco A, Prato M, Kostarelos K. Carbon nanotubes as nanomedicines: from toxicology to pharmacology. Adv Drug Deliv Rev 2006;58(14):1460-1470 (Pubitemid 44822607)
21. Kim Y, Dalhaimer P, Christian DA, Discher DE. Polymeric worm micelles as nano-carriers for drug delivery. Nanotechnology 2005;7:S484 (Pubitemid 40878515)
22. Liu Z, Robinson JT, Sun X, Dai H. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc 2008;130(33):10876-10877 • Demonstration of nanocarbon-mediated water-insoluble therapeutic delivery.
23. Liu Z, Sun X, Nakayama-Ratchford N, Dai H. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano 2007;1(1):50-56
24. Khan SA, Ivancic DZ, Zaichuk T, et al. Internalization and retention of nanodiamonds by MCF-7 cells in vitro: a potential drug delivery platform. Cancer Res 2009;69(2-MeetingAbstracts):2134
25. Vial S, Mansuy C, Saga S, et al. Peptide-grafted nanodiamonds: preparation, cytotoxicity and uptake in cells. ChemBioChem 2008;9(13):2113-2119
26. Faklaris O, Garrot D, Joshi V, et al. Detection of single photoluminescent diamond nanoparticles in cells and study of the internalization pathway. Small 2008;4(12):2236-2239
27. Neugart F, Zappe A, Jelezko F, et al. Dynamics of diamond nanoparticles in solution and cells. Nano Lett 2007;7(12):3588-3591
28. Yu SJ, Kang MW, Chang HC, et al. Bright fluorescent nanodiamonds: no photobleaching and low cytotoxicity. J Am Chem Soc 2005;127(50):17604-17605
29. Chang YR, Lee HY, Chen K, et al. Mass production and dynamic imaging of fluorescent nanodiamonds. Nat Nanotechnol 2008;3(5):284-288 •• Scalable nanodiamond imaging agent synthesis and intracellular fluorescence activity are demonstrated in this work. (Pubitemid 351668061)
30. Fu C-C, Lee H-Y, Chen K, et al. Characterization and application of single fluorescent nanodiamonds as cellular biomarkers. Proc Natl Acad Sci 2007;104(3):727-732 (Pubitemid 46154678)
31. Mochalin VN, Gogotsi Y. Wet chemistry route to hydrophobic blue fluorescent nanodiamond. J Am Chem Soc 2009;131(13):4594-4595 • This work demonstrates the unique surface and binding properties of the nanodiamond surface for possible biomedical applications.
32. Chao J-I, Perevedentseva E, Chung P-H, et al. Nanometer-sized diamond particle as a probe for biolabeling. Biophys J 2007;93(6):2199-2208 (Pubitemid 47437603)
33. Knight DS, White WB. Characterization of diamond films by Raman-spectroscopy. J Mater Res 1989;4(2):385-393
34. Cheng CY, Perevedentseva E, Tu JS, et al. Direct and in vitro observation of growth hormone receptor molecules in A549 human lung epithelial cells by nanodiamond labeling. Appl Phys Lett 2007;90(16):163903-163913 • Targeted fluorescent nanodiamond labeling is demonstrated in this work. (Pubitemid 46644894)
35. Kruger A, Liang YJ, Jarre G, Stegk J. Surface functionalisation of detonation diamond suitable for biological applications. J Mater Chem 2006;16(24):2322-2328 (Pubitemid 43880338)
36. Huang LC, Chang HC. Adsorption and immobilization of cytochrome c on nanodiamonds. Langmuir 2004;20(14):5879-5884
37. Yeap WS, Tan YY, Loh KP. Using detonation nanodiamond for the specific capture of glycoproteins. Anal Chem 2008;80(12):4659-4665 • Protein interactions with nanodiamonds were demonstrated in this work.
38. Ushizawa K, Sato Y, Mitsumori T, et al. Covalent immobilization of DNA on diamond and its verification by diffuse reflectance infrared spectroscopy. Chem Phys Lett 2002;351(1-2):105-108
39. Yang WS, Auciello O, Butler JE, et al. DNA-modified nanocrystalline diamond thin-films as stable, biologically active substrates. Nat Mater 2002;1(4):253-257
40. Kossovsky N, Gelman A, Hnatyszyn HJ, et al. Surface-modified diamond nanoparticles as antigen delivery vehicles. Bioconjug Chem 1995;6(5):507-511
41. Huang TS, Tzeng Y, Liu YK, et al. Immobilization of antibodies and bacterial binding on nanodiamond and carbon nanotubes for biosensor applications. Diamond Relat Mater 2004;13(4-8):1098-1102 (Pubitemid 38616426)
42. Hartl A, Schmich E, Garrido JA, et al. Protein-modified nanocrystalline diamond thin films for biosensor applications. Nat Mater 2004;3(10):736-742
43. Krueger A. New carbon materials: biological applications of functionalized nanodiamond materials. Chemistry 2008;14(5):1382-1390
44. Kruger A. Hard and soft: biofunctionalized diamond. Angew Chem-Int Ed 2006;45(39):6426-6427 • Prospects and discussion for the biological functionalization of nanodiamonds are discussed in this work, outlining the potential of nanodiamonds for biologically relevant applications.
45. Schrand AM, Hens SAC, Shenderova OA. Nanodiamond particles: properties and perspectives for bioapplications. Crit Rev Solid State Mater Sci 2009;34(1):18-74
46. Maynard AD, Baron PA, Foley M, et al. Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material. J Toxicol Environ Health Pt A 2004;67(1):87-107 (Pubitemid 38117533)
47. Warheit DB, Laurence BR, Reed KL, et al. Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 2004;77(1):117-125 (Pubitemid 38128651)
48. Lam C-W, James JT, McCluskey R, Hunter RL. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 2004;77(1):126-134 (Pubitemid 38128652)
49. Muller J, Huaux F, Moreau N, et al. Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 2005;207(3):221-231 (Pubitemid 41207915)
50. Singh R, Pantarotto D, Lacerda L, et al. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc Natl Acad Sci USA 2006;103(9):3357-3362 (Pubitemid 43346474)
51. Pantarotto D, Partidos CD, Hoebeke J, et al. Immunization with peptide-functionalized carbon nanotubes enhances virus-specific neutralizing antibody responses. Chem Biol 2003;10(10):961-966 (Pubitemid 37316913)
52. Schrand AM, Huang H, Carlson C, et al. Are diamond nanoparticles cytotoxic? J Phys Chem B 2007;111(1):2-7 • Insight into nanodiamond biocompatibility via MTT assays is provided in this study.
53. Liu KK, Cheng CL, Chang CC, Chao JI. Biocompatible and detectable carboxylated nanodiamond on human cell. Nanotechnology 2007;18(32):10
54. Schrand AM, Dai L, Schlager JJ, et al. Differential biocompatibility of carbon nanotubes and nanodiamonds. Diamond Relat Mater 2007;16(12):2118-2123 (Pubitemid 350117432)
55. Bakowicz K, Mitura S. Biocompatibility of NCD. J Wide Bandgap Mater 2002;9:261-272
56. Huang H, Pierstorff E, Osawa E, Ho D. Active nanodiamond hydrogels for chemotherapeutic delivery. Nano Lett 2007;7(11):3305-3314 •• Nanodiamond-mediated functionalization and release of a clinically relevant chemotherapeutic was introduced in this work. (Pubitemid 350216021)
57. Puzyr AP, Neshumayev DA, Tarskikh SV, et al. Destruction of human blood cells in interaction with detonation nanodiamonds in experiments in vitro. Diamond Relat Mater 2004;13(11-12):2020-2023
58. Eidelman ED, Siklitsky VI, Sharonova LV, et al. A stable suspension of single ultrananocrystalline diamond particles. Diamond Relat Mater 2005;14(11-12):1765-1769
59. Krueger A, Ozawa M, Jarre G, et al. Deagglomeration and functionalisation of detonation diamond. Phys Status Solidi (a) 2007;204(9):2881-2887
60. Yuan Y, Chen Y, Liu J-H, et al. Biodistribution and fate of nanodiamonds in vivo. Diamond Relat Mater 2009;18(1):95-100
61. Ranson MR, Carmichael J, O'Byrne K, et al. Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. J Clin Oncol 1997;15(10):3185-3191 (Pubitemid 27419330)
62. Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science 2004;303(5665):1818-1822 (Pubitemid 38374867)
63. Broz P, Driamov S, Ziegler J, et al. Toward intelligent nanosize bioreactors: a ph-switchable, channel-equipped, functional polymer nanocontainer. Nano Lett 2006;6(10):2349-2353 (Pubitemid 44663830)
64. Kruger A, Kataoka F, Ozawa M, et al. Unusually tight aggregation in detonation nanodiamond: identification and disintegration. Carbon 2005;43(8):1722-1730
65. Ozawa M, Inaguma M, Takahashi M, et al. Preparation and behavior of brownish, clear nanodiamond colloids. Adv Mater 2007;19(9):1201-1206 (Pubitemid 46942248)
66. Bondar VS, Puzyr AP. Nanodiamonds for biological investigations. Phys Solid State 2004;46(4):716-719
67. Barnard AS, Sternberg M. Crystallinity and surface electrostatics of diamond nanocrystals. J Mater Chem 2007;17(45):4811-4819 • Important findings characterizing the surface electrostatics of nanodiamond particles. (Pubitemid 350129396)
68. Barnard AS. Self-assembly in nanodiamond agglutinates. J Mater Chem 2008;18(34):4038-4041
69. Osawa E, Ho D, Huang H, et al. Consequences of strong and diverse electrostatic potential fields on the surface of detonation nanodiamond particles. Diamond Relat Mater 2009;18(5-8):904-909 • Surface electrostatic properties based on nanodiamond composition is addressed in this work, using drug-nanodiamond interactions as a specific model for validation and discussion.
70. Myrdal PB, Yalkowsky SH. Solubilization of drugs in aqueous media. In: Swarbrick J, Boylan JC, editors, Encyclopedia of pharmaceutical technology: CRC Press; New York, New York 2002. p. 2458-2480
71. Chen M, Pierstorff E, Lam R, et al. Nanodiamond-mediated delivery of water-insoluble therapeutics. ACS Nano 2009;(In press) doi: 10.1021/nn900480m
72. Sheihet L, Dubin RA, Devore D, Kohn J. Hydrophobic drug delivery by self-assembling triblock copolymer-derived nanospheres. Biomacromolecules 2005;6(5):2726-2731 (Pubitemid 41388286)
73. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 2005;97(22):1652-1662 (Pubitemid 41672231)
74. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90(18):1371-1388 (Pubitemid 28439961)
75. Kircheis R, Wightman L, Wagner E. Design and gene delivery activity of modified polyethylenimines. Adv Drug Deliv Rev 2001;53(3):341-358 (Pubitemid 34024914)
76. Bettinger T, Remy J-S, Erbacher P. Size reduction of galactosylated PEI/DNA complexes improves lectin-mediated gene transfer into hepatocytes. Bioconjug Chem 1999;10(4):558-561 (Pubitemid 29355232)
77. Kim K-H, Moldovan N, Espinosa Horacio D. A nanofountain probe with sub-100 nm molecular writing resolution13. Small 2005;1(6):632-635 (Pubitemid 43951742)
78. Loh O, Lam R, Chen M, et al. Nanofountain-probe-based high-resolution patterning and single-cell injection of functionalized nanodiamonds. Small 2009;(In press) doi: 10.1002/smll.200900361
79. Loh OY, Ho AM, Rim JE, et al. Electric field-induced direct delivery of proteins by a nanofountain probe. Proc Natl Acad Sci 2008;105(43):16438-16443
80. Jiang W, Kim BYS, Rutka JT, Chan WCW. Nanoparticle-mediated cellular response is size-dependent. Nat Nano 2008;3(3):145-150
81. Chen Y-C, Tzeng Y, Cheng A-J, et al. Inkjet printing of nanodiamond suspensions in ethylene glycol for CVD growth of patterned diamond structures and practical applications. Diamond Relat Mater 2009;18(2-3):146-150
82. Chen Y-C, Tzeng Y, Davray A, et al. Fabrication of diamond micro-structures by ink-jet printed diamond seeding and microwave plasma assisted chemical vapor deposition. Diamond Relat Mater 2008;17(4-5):722-727 (Pubitemid 351608833)
83. Langer R, Tirrell DA. Designing materials for biology and medicine. Nature 2004;428(6982):487-492
84. Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release 2001;73(2-3):121-136 (Pubitemid 32539245)
85. Moses MA, Brem H, Langer R. Advancing the field of drug delivery: taking aim at cancer. Cancer Cell 2003;4(5):337-341 (Pubitemid 37491094)
86. Peng L, Mendelsohn AD, LaTempa TJ, et al. Long-term small molecule and protein elution from TiO2 nanotubes. Nano Lett 2009;9(5):1932-1936
87. Santini JT, Richards AC, Scheidt R, et al. Microchips as controlled drug-delivery devices. Angew Chem Int Ed 2000;39(14):2396-2407
88. Lankelma J, Dekker H, Luque RF, et al. Doxorubicin gradients in human breast cancer. Clin Cancer Res 1999;5(7):1703-1707 (Pubitemid 29334449)
89. Tannock IF, Lee CM, Tunggal JK, et al. Limited penetration of anticancer drugs through tumor tissue: a potential cause of resistance of solid tumors to chemotherapy. Clin Cancer Res 2002;8(3):878-884
90. Peer D, Karp JM, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nat Nano 2007;2(12):751-760 •• A comprehensive review of the challenges associated with clinical translation of nanocarriers. (Pubitemid 350223348)
91. Adams GP, Schier R, McCall AM, et al. High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Res 2001;61(12):4750-4755 (Pubitemid 32691886)
92. Durand RE. Slow penetration of anthracyclines into spheroids and tumors: a therapeutic advantage? Cancer Chemother Pharmacol 1990;26(3):198-204
93. Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer 2006;6(8):583-592
94. Huang H, Pierstorff E, Osawa E, Ho D. Protein-mediated assembly of nanodiamond hydrogels into a biocompatible and biofunctional multilayer nanofilm. ACS Nano 2008;2(2):203-212 (Pubitemid 351585936)
95. Liu Y, Khabashesku VN, Halas NJ. Fluorinated nanodiamond as a wet chemistry precursor for diamond coatings covalently bonded to glass surface. J Am Chem Soc 2005;127(11):3712-3713 • A facile route towards generating stable and functionalized nanodiamond thin films is demonstrated in this work. (Pubitemid 40411408)
96. Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 1997;277(5330):1232-1237 (Pubitemid 27449063)
97. Tang Z, Wang Y, Podsiadlo P, Kotov NA. Biomedical applications of layer-by-layer assembly: from biomimetics to tissue engineering. Adv Mater 2006;18(24):3203-3224 (Pubitemid 46084822)
98. Lam R, Chen M, Pierstorff E, et al. Nanodiamond-embedded microfilm devices for localized chemotherapeutic elution. ACS Nano 2008;2(10):2095-2102 • This work introduced the scalable fabrication of nanodiamond-based drug delivery devices with demonstrated long-term release as well as suppression of burst chemotherapeutic delivery.
99. Behler KD, Stravato A, Mochalin V, et al. Nanodiamond-polymer composite fibers and coatings. ACS Nano 2009;3(2):363-369
100. Hanada K, Yamamoto K, Taguchi T, et al. Further studies on copper nanocomposite with dispersed single-digit-nanodiamond particles. Diamond Relat Mater 2007;16(12):2054-2057 (Pubitemid 350117429)
101. Yamagishi FG. Investigation of plasma-polymerized films as primers for parylene-c coatings on neural coatings on neural prosthesis materials. Thin Solid Films 1991;202(1):39-50
102. Schmidt EM, McIntosh JS, Bak MJ. Long-term implants of parylene-c coated microelectrodes. Med Biol Eng Comput 1988;26(1):96-101
103. Hahn AW, York DH, Nichols MF, et al. Biocompatibility of glow-discharge-polymerized films and vacuum-deposited parylene. Appl Polym Symp 1984;38:55-64
104. Chang TY, Yadav VG, De Leo S, et al. Cell and protein compatibility of parylene-C surfaces. Langmuir 2007;23(23):11718-11725 (Pubitemid 350133020)
105. Burkel WE, Kahn RH. Cell-lined, nonwoven microfiber scaffolds as a blood interface. Ann NY Acad Sci 1977;283(FEB10):419-437
106. Fortin JB, Lu TM. A model for the chemical vapor deposition of poly(para-xylylene) (parylene) thin films. Chem Mat 2002;14(5):1945-1949
107. Pierstorff E, Lam R, Ho D. Nanoscale architectural tuning of parylene patch devices to control therapeutic release rates. Nanotechnology 2008;44:445104
108. Robinson EM, Lam R, Pierstorff ED, Ho D. Localized therapeutic release via an amine-functionalized poly-p-xylene microfilm device. J Phys Chem B 2008;112(37):11451-11455
109. Chen M, Huang H, Pierstorff E, et al. Parylene-encapsulated copolymeric membranes as localized and sustained drug delivery platforms. Ann Biomed Eng 2009;(In press) doi: 10.1007/s10439-009-9662-9
110. Meng E, Yu-Chong T. Parylene etching techniques for microfluidics and bioMEMS. Micro Electro Mechanical Systems, 2005 MEMS 2005 18th IEEE International Conference on 2005. 568-571
111. Wong PK, Yu F, Shahangian A, et al. Closed-loop control of cellular functions using combinatory drugs guided by a stochastic search algorithm. Proc Natl Acad Sci 2008;105(13):5105-5110 (Pubitemid 351738517)
112. Lee J, Lilly GD, Doly RC, et al. In vitro toxicity testing of nanoparticles in 3D cell culture. Small 2009;5(10):1213-1221
113. Sutherland RM. Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 1988;240(4849):177-184
114. Choi HS, Ipe BI, Misra P, et al. Tissue- and organ-selective biodistribution of NIR fluorescent quantum dots. Nano Lett 2009;9(6):2354-2359
115. Oberdorster G, Stone V, Donaldson K. Toxicology of nanoparticles: a historical perspective. Nanotoxicology 2007;1(1):2-25
116. Lyon DY, Alvarez PJJ. Fullerene water suspension (nC(60)) exerts antibacterial effects via ROS-independent protein oxidation. Environ Sci Technol 2008;42(21):8127-8132
117. Cagle DW, Kennel SJ, Mirzadeh S, et al. In vivo studies of fullerene-based materials using endohedral metallofullerene radiotracers. Proc Natl Acad Sci USA 1999;96(9):5182-5187
118. Yamago S, Tokuyama H, Nakamura E, et al. In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity. Chem Biol 1995;2(6):385-389
119. Miyawaki J, Matsumura S, Yuge R, et al. Biodistribution and ultrastructural localization of single-walled carbon nanohorns determined in vivo with embedded Gd2O3 labels. ACS Nano 2009;3(6):1399-406 • Biodistribution and accumulation of carbon nanomaterials in vivo are studied in this work, providing a foundation for continued biocompatibility analysis.