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

Biomacromolecules. 2017 Jan 9;18(1):249-256. doi: 10.1021/acs.biomac.6b01568. Epub 2016 Dec 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boron / chemistry*
  • Colonic Neoplasms / pathology*
  • Coloring Agents / chemistry*
  • Hyaluronic Acid / chemistry
  • Indocyanine Green / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Optical Imaging / methods*
  • Photoacoustic Techniques / methods*
  • Polymers / chemistry*
  • Spectroscopy, Near-Infrared
  • Tumor Cells, Cultured

Substances

  • Coloring Agents
  • Polymers
  • Hyaluronic Acid
  • Indocyanine Green
  • Boron