title: Tumor specific liposomes improve detection of pancreatic adenocarcinoma in vivo using optoacoustic tomography.
abstract: BACKGROUND
  Pancreatic cancer often goes undiagnosed until late stage disease due in part to suboptimal early detection. Our goal was to develop a Syndecan-1 tagged liposome containing fluorescent dye as an improved contrast agent for detection of pancreatic adenocarcinoma in vivo using multispectral optoacoustic tomography.
  
  
  RESULTS
  The diagnostic capabilities and specificity to pancreatic adenocarcinoma of Syndecan-1 targeted liposomes were evaluated both in vitro and in vivo. Immunocytochemistry showed that liposomes preferentially bound to and released their contents into cells expressing high levels of insulin-like growth factor 1 receptor. We determined that the contents of the liposome were released into the cell as noted by the change in propidium iodide fluorescence from green to red based upon nucleic acid binding. In an orthotopic mouse model, the liposomes preferentially targeted the pancreatic tumor with little off-target binding in the liver and spleen. Peak accumulation of the liposomes in the tumor occurred at 8 h post-injection. Multispectral optoacoustic tomographic imaging was able to provide high-resolution 3D images of the tumor and liposome location. Ex vivo analysis showed that non-targeted liposomes accumulated in the liver, suggesting that specificity of the liposomes for pancreatic adenocarcinoma was due to the presence of the Syndecan-1 ligand.
  
  
  CONCLUSIONS
  This study demonstrated that Syndecan-1 liposomes were able to release cargo into IGF1-R expressing tumor cells. The Syndecan-1 liposomes demonstrated tumor specificity in orthotopic pancreatic cancer as observed using multispectral optoacoustic tomography with reduced kidney and liver uptake. By targeting the liposome with Syndecan-1, this nanovehicle has potential as a targeted theranostic nanoparticle for both drug and contrast agent delivery to pancreatic tumors.
authors.affiliation: University of Louisville, 505 S Hancock, Louisville, KY, 40202, USA. wenyuan.yin@louisville.edu.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Yin
authors.affiliation: University of Louisville, 505 S Hancock, Louisville, KY, 40202, USA. charles.kimbrough@louisville.edu.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Kimbrough
authors.affiliation: University of Louisville, 505 S Hancock, Louisville, KY, 40202, USA. jorge.gutierrez@louisville.edu.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Gomez-Gutierrez
authors.affiliation: University of Louisville, 505 S Hancock, Louisville, KY, 40202, USA. christopher.burns@louisville.edu.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Burns
authors.affiliation: University of Louisville, 505 S Hancock, Louisville, KY, 40202, USA. phillip.chuong@louisville.edu.
authors.forename: Phillip
authors.initials: P
authors.lastname: Chuong
authors.affiliation: University of Alabama Birmingham, ZRB 408, 1720 2nd Avenue South, Birmingham, AL, 35294, USA. wgrizzle@uabmc.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.affiliation: University of Louisville, 505 S Hancock, Louisville, KY, 40202, USA. Lrmcna01@louisville.edu.
authors.forename: Lacey R
authors.initials: LR
authors.lastname: McNally
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes; D015870:Gene Expression; D006801:Humans; D008081:Liposomes / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D061088:Photoacoustic Techniques / Q000379:methods; D011485:Protein Binding; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D053668:Syndecan-1 / Q000737:chemistry / Q000378:metabolism*; D014054:Tomography / Q000295:instrumentation / Q000379:methods
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D008081:Liposomes; D017451:Receptors, Somatomedin; D053668:Syndecan-1