title: Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines.
abstract: There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and provide good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ∼ 20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1,000). Unlike conventional chromophores, nanonaps exhibit non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole-body imaging.
authors.affiliation: 1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Yumiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Department of Creative IT Engineering, POSTECH, Pohang, Korea.
authors.forename: Mansik
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Rich
authors.affiliation: Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Jumin
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Sixiang
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Paschalis
authors.initials: P
authors.lastname: Alexandridis
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Huizinga
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Mukund
authors.initials: M
authors.lastname: Seshadri
authors.affiliation: Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.affiliation: 1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Department of Creative IT Engineering, POSTECH, Pohang, Korea.
authors.forename: Chulhong
authors.initials: C
authors.lastname: Kim
authors.affiliation: 1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
mesh_terms: D000818:Animals; D004396:Coloring Agents; D005260:Female; D005615:Freezing; D007422:Intestines / Q000473:pathology* / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008823:Micelles; D064847:Multimodal Imaging / Q000379:methods; D053758:Nanoparticles; D061088:Photoacoustic Techniques / Q000379:methods; D011166:Porphyrins; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D004396:Coloring Agents; D008823:Micelles; D011166:Porphyrins; C076388:2,3-naphthalocyanine