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The Effect of Sonication on Extravasation and Distribution of Nanoparticles and Dextrans in Tumor Tissue Imaged by Multiphoton Microscopy

The Effect of Sonication on Extravasation and Distribution of Nanoparticles and Dextrans in Tumor Tissue Imaged by Multiphoton Microscopy

Category
Journal publication
Abstract
Ultrasound (US)and systemic administration of microbubbles (MBs)have been shown to improve the delivery of drugs and nanoparticles (NPs)to tumor tissue. A better understanding of the mechanisms is crucial for effective delivery of NPs and drugs. To elucidate the kinetics of extravasation events, and relate it to the vessel diameter and flow, we have performed real-time intravital multiphoton microscopy during US sonication of tumors growing in dorsal window chambers. We studied the effects of four different mechanical index (MI)levels (0.2 to 0.8)while injecting SonoVue or in-house made MBs with NPs in the shell (NPMB). We found that high MI of 0.8 induced a violent extravasation of both NPs and dextrans. Using lower MIs (0.2-0.6), less extravasation was detected and it occurred in vessels with larger diameters compared to sonication at MI 0.8. The rate of extravasation of both NPs and dextrans, and the displacement of NPs and dextrans from the vessel into the tumor tissue, correlated with MI. The observed extravasation events happened within milliseconds to minutes after the US exposure started. Moreover, we have observed a change of blood flow rate and direction with all the MIs tested
Client
  • Norges forskningsråd / 240316
Language
English
Author(s)
  • Yemane Petros Tesfamichael
  • Åslund Andreas
  • Sæterbø Kristin Grendstad
  • Bjørkøy Astrid
  • Snipstad Sofie
  • van Wamel Annemieke
  • Berg Sigrid
  • Mørch Ýrr Asbjørg
  • Hansen Rune
  • Angelsen Bjørn Atle Johan
  • Davies Catharina de Lange
Affiliation
  • Norwegian University of Science and Technology
  • St. Olavs Hospital, Trondheim University Hospital
  • SINTEF Digital / Health Research
  • Norwegian University of Science and Technology
  • SINTEF Industry / Biotechnology and Nanomedicine
Year
2018
Published in
Proceedings - IEEE Ultrasonics Symposium
ISSN
1948-5719
Publisher
IEEE Geoscience and Remote Sensing Society
Volume
2018
Booklet
October