Impact of fluorescent dyes on the physicochemical parameters of microbubbles stabilized by albumin-dye complex

Roman A. Barmin, Polina G. Rudakovskaya, Vasiliy S. Chernyshev, Olga I. Guslyakova, Olga A. Sindeeva, Ekaterina S. Prikhozhdenko, Daniil N. Bratashov, Arkady S. Abdurashitov, Elizaveta A. Maksimova, Polina A. Demina, Evgeny V. Khaydukov, Alexey V. Gayer, Evgeny A. Shirshin, Alexander A. Solovev, Yongfeng Mei, Dmitry A. Gorin

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Gas-filled microbubbles are routinely used as ultrasound contrast agents in the clinic. Recently, microbubbles attracted attention as agents for multimodal imaging and image-guided drug delivery. Hence, we prepared microbubbles based on albumin-dye complexes to achieve optimal bimodal (fluorescent/ultrasound) imaging properties. The fluorescent dyes used for in vitro/in vivo/medical imaging (Fluorescein, and Rhodamine B, Cyanine 5.5, and Cyanine 7, Indocyanine Green) were introduced into the albumin-dye complex structure. Interconnections between dyes parameters (chemical structure, molecular weight, and hydrophobicity), properties of albumin-dye complexes (type of bond and ratio between protein and dye, solution surface tension), and bimodal agent properties (concentration, mean size, storage stability) were evaluated. Bimodal imaging of “colored” microbubbles was assessed using ultrasound with 33, 50 MHz frequencies and fluorescence tomography. We observed that the ratio between the protein molecules and the protein-dye complex in the microbubble shell was approximately equal, highlighting the impact of dye chemical structure on albumin-dye complex properties and resulting microbubble properties in characterization and imaging. These findings shed light on correlations between microbubble interface stabilization with albumin, microbubble structure formed by albumin-dye complexes, physicochemical properties and applications of bimodal (fluorescent/ultrasound) contrast agents.

Original languageEnglish
Article number129095
JournalColloids and Surfaces A: Physicochemical and Engineering Aspects
Publication statusPublished - 20 Aug 2022


  • Bovine serum albumin
  • Fluorescence imaging
  • Fluorescent dyes
  • Gas/liquid interface
  • Microbubbles
  • Ultrasound imaging


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