title: Polymeric Self-Assemblies with Boron-Containing Near-Infrared Dye Dimers for Photoacoustic Imaging Probes.
abstract: Polymers containing pyrrolopyrrole aza-BODIPY (PPAB) and thiophene-bridged BODIPY dimers (TBD) having poly(ethylene glycol) (PEG) or PEGylated hyaluronic acid (HA) were prepared by facile conjugation approaches. Self-assemblies consisting of TBD-conjugated polymers more efficiently generated photoacoustic (PA) signals than PPAB-PEG conjugate upon irradiation with near-infrared pulsed laser light. Among dye-conjugated polymers examined, TBD-HA-PEG conjugates efficiently generated photoacoustic signals, 1.49-1.83 times stronger than that of commercially available indocyanine green (ICG). We found that the following two factors are essential to enhance PA signals from self-assemblies: (1) the formation of strongly interacting TBD aggregates and (2) enhancement of the elastic modulus of self-assemblies by conjugating TBDs with HA. TBD-conjugated HA derivatives circulated in blood vessels for a longer time (15.6 ± 4.9% injected dose (ID) in blood 24 h after injection) and more specifically accumulated in tumor tissues (17.8 ± 3.5% ID/g in tumor 24 h after injection) than ICG-conjugated HA derivatives, visualizing a tumor site more clearly. The cell uptake experiment of dye-HA conjugates indicates that ICG-conjugated polymers internalized into cells or merged with cell walls to emit strong fluorescence, while TBD-conjugated polymers were not internalized into cells. Because the disassembly of the TBD-conjugated HA derivatives is suppressed, aggregated TBDs emit weak fluorescence but efficiently generate strong PA signals in tumor tissues.
authors.forename: Koji
authors.initials: K
authors.lastname: Miki
authors.forename: Akane
authors.initials: A
authors.lastname: Enomoto
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Graduate School of Pure and Applied Sciences and Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Graduate School of Pure and Applied Sciences and Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan.
authors.forename: Sousuke
authors.initials: S
authors.lastname: Saino
authors.affiliation: Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University , Fukuoka 819-0395, Japan.
authors.forename: Soji
authors.initials: S
authors.lastname: Shimizu
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Kouichi
authors.identifier: 0000-0001-8893-8893
authors.initials: K
authors.lastname: Ohe
mesh_terms: D000818:Animals; D001895:Boron / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000473:pathology*; D004396:Coloring Agents / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry; D007208:Indocyanine Green / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D061088:Photoacoustic Techniques / Q000379:methods*; D011108:Polymers / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared; D014407:Tumor Cells, Cultured
chemical_list: D004396:Coloring Agents; D011108:Polymers; D006820:Hyaluronic Acid; D007208:Indocyanine Green; D001895:Boron