Filled and glycosylated carbon nanotubes for in vivo radioemitter localization and imaging.
Functionalization of nanomaterials for precise biomedical function is an emerging trend in nanotechnology. Carbon nanotubes are attractive as multifunctional carrier systems because payload can be encapsulated in internal space whilst outer surfaces can be chemically modified. Yet, despite potential as drug delivery systems and radiotracers, such filled-and-functionalized carbon nanotubes have not been previously investigated in vivo. Here we report covalent functionalization of radionuclide-filled single-walled carbon nanotubes and their use as radioprobes. Metal halides, including Na(125)I, were sealed inside single-walled carbon nanotubes to create high-density radioemitting crystals and then surfaces of these filled-sealed nanotubes were covalently modified with biantennary carbohydrates, improving dispersibility and biocompatibility. Intravenous administration of Na(125)I-filled glyco-single-walled carbon nanotubes in mice was tracked in vivo using single-photon emission computed tomography. Specific tissue accumulation (here lung) coupled with high in vivo stability prevented leakage of radionuclide to high-affinity organs (thyroid/stomach) or excretion, and resulted in ultrasensitive imaging and delivery of unprecedented radiodose density. Nanoencapsulation of iodide within single-walled carbon nanotubes enabled its biodistribution to be completely redirected from tissue with innate affinity (thyroid) to lung. Surface functionalization of (125)I-filled single-walled carbon nanotubes offers versatility towards modulation of biodistribution of these radioemitting crystals in a manner determined by the capsule that delivers them. We envisage that organ-specific therapeutics and diagnostics can be developed on the basis of the nanocapsule model described here.
Hong
Sung You
SY
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
Tobias
Gerard
G
Al-Jamal
Khuloud T
KT
Ballesteros
Belén
B
Ali-Boucetta
Hanene
H
Lozano-Perez
Sergio
S
Nellist
Peter D
PD
Sim
Robert B
RB
Finucane
Ciara
C
Mather
Stephen J
SJ
Green
Malcolm L H
ML
Kostarelos
Kostas
K
Davis
Benjamin G
BG
D000117:Acetylglucosamine / Q000378:metabolism; D050260:Carbohydrate Metabolism; D006031:Glycosylation; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D017348:Microscopy, Electron, Scanning Transmission / Q000379:methods; D036103:Nanotechnology / Q000379:methods / Q000639:trends*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010084:Oxidation-Reduction; D011868:Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D013270:Stomach / Q000000981:diagnostic imaging; D013961:Thyroid Gland / Q000000981:diagnostic imaging; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed / Q000379:methods
D037742:Nanotubes, Carbon; D011868:Radioisotopes; D000117:Acetylglucosamine
Nat Nanotechnol. 2007 Jul;2(7):422-5
18654326
J Am Chem Soc. 2007 Sep 12;129(36):10966-7
17696530
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1410-5
18230737
Nat Rev Drug Discov. 2003 Jan;2(1):29-37
12509757
Chem Rev. 1996 Mar 28;96(2):683-720
11848770
Science. 2007 May 11;316(5826):853
17322029
Chem Rev. 2002 Feb;102(2):579-602
11841255
Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7053s-7063s
16203802
J Am Chem Soc. 2006 May 17;128(19):6292-3
16683774
Glycobiology. 1993 Apr;3(2):97-130
8490246
Acc Chem Res. 2008 Jan;41(1):60-8
17867649
Small. 2008 Sep;4(9):1501-6
18702121
J Leukoc Biol. 2004 Jan;75(1):27-33
12972515
Angew Chem Int Ed Engl. 2005 Oct 7;44(39):6358-62
16138384
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12371-6
16895981
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3357-62
16492781
Nat Biotechnol. 2008 Jul;26(7):774-6
18612299
Small. 2007 Sep;3(9):1496-9
17668431
J Infect Dis. 1988 Aug;158(2):407-14
3042877
J Am Chem Soc. 2009 Jan 28;131(3):890-1
19119844
Nat Nanotechnol. 2007 Jan;2(1):47-52
18654207
Phys Med Biol. 2008 May 7;53(9):2233-52
18401059
Science. 1998 Oct 2;282(5386):95-8
9756485
Mol Imaging Biol. 2009 May-Jun;11(3):195-203
19048346
Angew Chem Int Ed Engl. 2008;47(27):5022-5
18509843
Science. 2000 Aug 25;289(5483):1324-7
10958773
Nat Biotechnol. 2005 Nov;23(11):1418-23
16244656
Gene Ther. 2001 Oct;8(20):1524-31
11704812
J Biol Chem. 2004 Oct 15;279(42):43990-7
15302866
J Nucl Med. 2007 Jul;48(7):1180-9
17607040
J Pharm Sci. 1980 Jul;69(7):755-62
7391933
Eur J Nucl Med Mol Imaging. 2002 Jul;29(7):933-8
12111135