title: Porphyrin Nanodroplets: Sub-micrometer Ultrasound and Photoacoustic Contrast Imaging Agents.
abstract: A novel class of all-organic nanoscale porphyrin nanodroplet agents is presented which is suitable for multimodality ultrasound and photoacoustic molecular imaging. Previous multimodality photoacoustic-ultrasound agents are either not organic, or not yet demonstrated to exhibit enhanced accumulation in leaky tumor vasculature, perhaps because of large diameters. In the current study, porphyrin nanodroplets are created with a mean diameter of 185 nm which is small enough to exhibit the enhanced permeability and retention effect. Porphyrin within the nanodroplet shell has strong optical absorption at 705 nm with an estimated molar extinction coefficient >5 × 10(9) m(-1) cm(-1) , allowing both ultrasound and photoacoustic contrast in the same nanoparticle using all organic materials. The potential of nanodroplets is that they may be phase-changed into microbubbles using high pressure ultrasound, providing ultrasound contrast with single-bubble sensitivity. Multispectral photoacoustic imaging allows visualization of nanodroplets when injected intratumorally in an HT1080 tumor in the chorioallantoic membrane of a chicken embryo. Intravital microscopy imaging of Hep3-GFP and HT1080-GFP tumors in chicken embryos determines that nanodroplets accumulated throughout or at the periphery of tumors, suggesting that porphyrin nanodroplets may be useful for enhancing the visualization of tumors with ultrasound and/or photoacoustic imaging.
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Paproski
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Forbrich
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Huynh
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, T6G2J7, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4, Canada.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Zemp
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D003287:Contrast Media / Q000737:chemistry*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007834:Lasers; D045423:Microbubbles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D061088:Photoacoustic Techniques / Q000379:methods*; D011166:Porphyrins / Q000737:chemistry*; D014465:Ultrasonics / Q000379:methods*
chemical_list: D003287:Contrast Media; D011166:Porphyrins
keywords: nanodroplets; photoacoustics; porphyrin; ultrasound