title: Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes.
abstract: Highly sensitive detection of small, deep tumors for early diagnosis and surgical interventions remains a challenge for conventional imaging modalities. Second-window near-infrared light (NIR2, 950-1,400 nm) is promising for in vivo fluorescence imaging due to deep tissue penetration and low tissue autofluorescence. With their intrinsic fluorescence in the NIR2 regime and lack of photobleaching, single-walled carbon nanotubes (SWNTs) are potentially attractive contrast agents to detect tumors. Here, targeted M13 virus-stabilized SWNTs are used to visualize deep, disseminated tumors in vivo. This targeted nanoprobe, which uses M13 to stably display both tumor-targeting peptides and an SWNT imaging probe, demonstrates excellent tumor-to-background uptake and exhibits higher signal-to-noise performance compared with visible and near-infrared (NIR1) dyes for delineating tumor nodules. Detection and excision of tumors by a gynecological surgeon improved with SWNT image guidance and led to the identification of submillimeter tumors. Collectively, these findings demonstrate the promise of targeted SWNT nanoprobes for noninvasive disease monitoring and guided surgery.
authors.affiliation: Koch Institute for Integrative Cancer Research, Departments of Materials Science and Engineering.
authors.forename: Debadyuti
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: Koch Institute for Integrative Cancer Research, Biophysics Program, Harvard University, Boston, MA 02115; MD-PhD Program, Harvard Medical School, Boston, MA 02115; and.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Bagley
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Young Jeong
authors.initials: YJ
authors.lastname: Na
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.affiliation: Koch Institute for Integrative Cancer Research, Harvard-MIT Division of Health Sciences and Technology, Electrical Engineering and Computer Science, and Institute for Medical Engineering and Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139; belcher@mit.edu sbhatia@mit.edu.
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
authors.affiliation: Koch Institute for Integrative Cancer Research, Departments of Materials Science and Engineering, Biological Engineering, belcher@mit.edu sbhatia@mit.edu.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Belcher
mesh_terms: D000818:Animals; D017104:Bacteriophage M13 / Q000737:chemistry*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D061848:Optical Imaging; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D037742:Nanotubes, Carbon; D010455:Peptides
keywords: M13 bacteriophage; cancer imaging; fluorescence-guided surgery