title: Near infrared fluorescent imaging of brain tumor with IR780 dye incorporated phospholipid nanoparticles.
abstract: Near-IR fluorescence (NIRF) imaging is becoming a promising approach in preclinical tumor detection and clinical image-guided oncological surgery. While heptamethine cyanine dye IR780 has excellent tumor targeting and imaging potential, its hydrophobic property limits its clinical use. In this study, we developed nanoparticle formulations to facilitate the use of IR780 for fluorescent imaging of malignant brain tumor.
  
  
  
  Self-assembled IR780-liposomes and IR780-phospholipid micelles were prepared and their NIRF properties were characterized. The intracellular accumulation of IR780-nanoparticles in glioma cells were determined using confocal microscopy. The in vivo brain tumor targeting and NIRF imaging capacity of IR780-nanoparticles were evaluated using U87MG glioma ectopic and orthotopic xenograft models and a spontaneous glioma mouse model driven by RAS/RTK activation.
  
  
  
  The loading of IR780 into liposomes or phospholipid micelles was efficient. The particle diameter of IR780-liposomes and IR780-phospholipid micelles were 95 and 26 nm, respectively. While stock solutions of each preparation were maintained at ready-to-use condition, the IR780-phospholipid micelles were more stable. In tissue culture cells, IR780-nanoparticles prepared by either method accumulated in mitochondria, however, in animals the IR780-phospholipid micelles showed enhanced intra-tumoral accumulation in U87MG ectopic tumors. Moreover, IR780-phospholipid micelles also showed preferred intracranial tumor accumulation and potent NIRF signal intensity in glioma orthotopic models at a real-time, non-invasive manner.
  
  
  
  The IR780-phospholipid micelles demonstrated tumor-specific NIRF imaging capacity in glioma preclinical mouse models, providing great potential for clinical imaging and image-guided surgery of brain tumors.
authors.affiliation: Small Animal Imaging Facility, Van Andel Research Institute, Grand Rapids, MI, 49503, USA. lishhchem@126.com.
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Cell and Cancer Biology, Van Andel Research Institute, Grand Rapids, MI, 49503, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Small Animal Imaging Facility, Van Andel Research Institute, Grand Rapids, MI, 49503, USA.
authors.forename: Anderson
authors.initials: A
authors.lastname: Peck
authors.affiliation: Center for Cell and Cancer Biology, Van Andel Research Institute, Grand Rapids, MI, 49503, USA. xieq01@etsu.edu.|Department of Biomedical Science, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA. xieq01@etsu.edu.|Center for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA. xieq01@etsu.edu.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xie
mesh_terms: D065638:Absorption, Radiation; D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology; D003199:Computer Systems; D004705:Endocytosis; D005910:Glioma / Q000175:diagnosis / Q000473:pathology; D007211:Indoles / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008819:Mice, Nude; D008823:Micelles; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D007211:Indoles; D008081:Liposomes; D008823:Micelles; D010743:Phospholipids
keywords: Blood–brain barrier; Brain tumor; Liposomes; Near infrared fluorescence imaging; Phospholipid micelles