Enhanced capillary delivery with nanobubble-mediated blood-brain barrier opening and advanced high resolution vascular segmentation

Roni Gattegno, Lilach Arbel, Noa Riess, Hila Shinar, Sharon Katz, Tali Ilovitsh

Research output: Contribution to journalArticlepeer-review

Abstract

Overcoming the blood-brain barrier (BBB) is essential to enhance brain therapy. Here, we utilized nanobubbles with focused ultrasound for targeted and improved BBB opening in mice. A microscopy technique method assessed BBB opening at a single blood vessel resolution employing a dual-dye labeling technique using green fluorescent molecules to label blood vessels and Evans blue brain-impermeable dye for quantifying BBB extravasation. A deep learning architecture enabled blood vessels segmentation, delivering comparable accuracy to manual segmentation with a significant time reduction. Segmentation outcomes were applied to the Evans blue channel to quantify extravasation of each blood vessel. Results were compared to microbubble-mediated BBB opening, where reduced extravasation was observed in capillaries with a diameter of 2–6 μm. In comparison, nanobubbles yield an improved opening in these capillaries, and equivalent efficacy to that of microbubbles in larger vessels. These results indicate the potential of nanobubbles to serve as enhanced agents for BBB opening, amplifying bioeffects in capillaries while preserving comparable opening in larger vessels.

Original languageEnglish
Pages (from-to)506-516
Number of pages11
JournalJournal of Controlled Release
Volume369
DOIs
StatePublished - May 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 Elsevier B.V.

Keywords

  • BBB opening
  • Focused ultrasound
  • Micobubbles
  • Nanobubbles
  • Nanotechnology

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