2. Academic Validation
  3. Copper-Catalyzed Covalent Dimerization of Near-Infrared Fluorescent Cyanine Dyes: Synergistic Enhancement of Photoacoustic Signals for Molecular Imaging of Tumors

Copper-Catalyzed Covalent Dimerization of Near-Infrared Fluorescent Cyanine Dyes: Synergistic Enhancement of Photoacoustic Signals for Molecular Imaging of Tumors

  • Anal Sens. 2022 Jan;2(1):e202100045. doi: 10.1002/anse.202100045.
Dolonchampa Maji 1 2,  Donghyeon Oh 3,  Krishna Sharmah Gautam 1,  Mingzhou Zhou 1,  Haini Zhang 1 2,  Jeff Kao 4,  Daryl Giblin 4,  Matthew Smith 1,  Junha Lim 5,  Seunghyun Lee 3,  Youngnam Kang 5,  Won Jong Kim 6,  Chulhong Kim 3,  Samuel Achilefu 1 2 7
Affiliations

Affiliations

  • 1 Optical Radiology Lab, Department of Radiology Washington University School of Medicine St. Louis, MO 63110 (USA).
  • 2 Department of Biomedical Engineering Washington University in St. Louis St. Louis, MO 63130 (USA).
  • 3 Department of Electrical Engineering, Convergence IT Engineering, and Mechanical Engineering, Medical Device Innovation Center Pohang University of Science and Technology (POSTECH) Pohang, 37673 (Republic of Korea).
  • 4 Department of Chemistry Washington University in St. Louis St. Louis, MO 63130 (USA).
  • 5 School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology (POSTECH) Pohang, 37673 (Republic of Korea).
  • 6 Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang, 37673 (Republic of Korea).
  • 7 Department of Medicine Washington University School of Medicine St. Louis, MO 63110 (USA).
PMID: 37621644 DOI: 10.1002/anse.202100045
Abstract

Photoacoustic (PA) imaging relies on the absorption of light by chromophores to generate acoustic waves used to delineate tissue structures and physiology. Here, we demonstrate that Cu(II) efficiently catalyzes the dimerization of diverse near-infrared (NIR) cyanine molecules, including a peptide conjugate. NMR spectroscopy revealed a C-C covalent bond along the heptamethine chains, creating stable molecules under conditions such as a wide range of Solvents and pH mediums. Dimerization achieved >90% fluorescence quenching, enhanced photostability, and increased PA signals by a factor of about 4 at equimolar concentrations compared to the monomers. In vivo study with a mouse Cancer model revealed that dimerization enhanced tumor retention and PA signal, allowing Cancer detection at doses where the monomers are less effective. While the dye dimers highlighted peritumoral blood vessels, the PA signal for dimeric tumor-targeting dye-peptide conjugate, LS301, was diffuse throughout the entire tumor mass. A combination of the ease of synthesis, diversity of molecules that are amenable to Cu(II)-catalyzed dimerization, and the high acoustic wave amplification by these stable dimeric small molecules ushers a new strategy to develop clinically translatable PA molecular amplifiers for the emerging field of molecular photoacoustic imaging.

Keywords

cyanine dyes; dimerization; fluorescence; photoacoustic imaging; tumors.

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