title: In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes.
abstract: Single-walled carbon nanotubes are particularly attractive for biomedical applications, because they exhibit a fluorescent signal in a spectral region where there is minimal interference from biological media. Although single-walled carbon nanotubes have been used as highly sensitive detectors for various compounds, their use as in vivo biomarkers requires the simultaneous optimization of various parameters, including biocompatibility, molecular recognition, high fluorescence quantum efficiency and signal transduction. Here we show that a polyethylene glycol ligated copolymer stabilizes near-infrared-fluorescent single-walled carbon nanotubes sensors in solution, enabling intravenous injection into mice and the selective detection of local nitric oxide concentration with a detection limit of 1 µM. The half-life for liver retention is 4 h, with sensors clearing the lungs within 2 h after injection, thus avoiding a dominant route of in vivo nanotoxicology. After localization within the liver, it is possible to follow the transient inflammation using nitric oxide as a marker and signalling molecule. To this end, we also report a spatial-spectral imaging algorithm to deconvolute fluorescence intensity and spatial information from measurements. Finally, we demonstrate that alginate-encapsulated single-walled carbon nanotubes can function as implantable inflammation sensors for nitric oxide detection, with no intrinsic immune reactivity or other adverse response for more than 400 days.
authors.affiliation: 1] Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [2] Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Iverson
authors.forename: Paul W
authors.initials: PW
authors.lastname: Barone
authors.forename: Mia
authors.initials: M
authors.lastname: Shandell
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Trudel
authors.forename: Selda
authors.initials: S
authors.lastname: Sen
authors.forename: Fatih
authors.initials: F
authors.lastname: Sen
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Ivanov
authors.forename: Esha
authors.initials: E
authors.lastname: Atolia
authors.forename: Edgardo
authors.initials: E
authors.lastname: Farias
authors.forename: Thomas P
authors.initials: TP
authors.lastname: McNicholas
authors.forename: Nigel
authors.initials: N
authors.lastname: Reuel
authors.forename: Nicola M A
authors.initials: NM
authors.lastname: Parry
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Wogan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Strano
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods*; D004247:DNA / Q000737:chemistry; D007249:Inflammation / Q000473:pathology; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry; D026361:Reactive Nitrogen Species / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D008024:Ligands; D037742:Nanotubes, Carbon; D011108:Polymers; D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D004247:DNA