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Polymeric Self-Assemblies with Boron-Containing Near-Infrared Dye Dimers for Photoacoustic Imaging Probes

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journal contribution
posted on 28.11.2016, 00:00 by Koji Miki, Akane Enomoto, Tatsuhiro Inoue, Tatsuya Nabeshima, Sousuke Saino, Soji Shimizu, Hideki Matsuoka, Kouichi Ohe
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.