title: Indocyanine green-loaded nanoparticles for image-guided tumor surgery.
abstract: Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye to tumors. Self-assembly of the nanoparticles was driven by conjugation of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5β-cholanamide (5βCA), or octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical properties were characterized. NanoICG exhibited quenched fluorescence that could be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic at physiologically relevant concentrations and exposure was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong fluorescence enhancement in tumors was observed with NanoICG using a fluorescence image-guided surgery system and a whole-animal imaging system. Tumor contrast with NanoICG was significantly higher than with ICG alone.
authors.affiliation: Virginia Tech - Wake Forest University School of Biomedical Engineering and Sciences, ‡Wake Forest Institute for Regenerative Medicine, §Department of Cancer Biology, Wake Forest University Health Sciences , Winston-Salem, North Carolina 27157, United States ;
authors.forename: Tanner K
authors.initials: TK
authors.lastname: Hill
authors.forename: Asem
authors.initials: A
authors.lastname: Abdulahad
authors.forename: Sneha S
authors.initials: SS
authors.lastname: Kelkar
authors.forename: Frank C
authors.initials: FC
authors.lastname: Marini
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Long
authors.forename: James M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Mohs
mesh_terms: D000818:Animals; D001940:Breast / Q000473:pathology / Q000601:surgery; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000601:surgery*; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D007208:Indocyanine Green / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D025321:Surgery, Computer-Assisted / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D006820:Hyaluronic Acid; D007208:Indocyanine Green