Quantitative Pharmacokinetics Reveal Impact of Lipid Composition on Microbubble and Nanoprogeny Shell Fate.

Autor: Rajora MA; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada.; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5G 1L7, Canada., Dhaliwal A; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada., Zheng M; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada., Choi V; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada., Overchuk M; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada.; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, 27599, USA., Lou JWH; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada., Pellow C; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.; Sunnybrook Research Institute, Toronto, Ontario, M4N 3M5, Canada., Goertz D; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.; Sunnybrook Research Institute, Toronto, Ontario, M4N 3M5, Canada., Chen J; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada., Zheng G; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada.; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Jan; Vol. 11 (4), pp. e2304453. Date of Electronic Publication: 2023 Nov 30.
DOI: 10.1002/advs.202304453
Abstrakt: Microbubble-enabled focused ultrasound (MB-FUS) has revolutionized nano and molecular drug delivery capabilities. Yet, the absence of longitudinal, systematic, quantitative studies of microbubble shell pharmacokinetics hinders progress within the MB-FUS field. Microbubble radiolabeling challenges contribute to this void. This barrier is overcome by developing a one-pot, purification-free copper chelation protocol able to stably radiolabel diverse porphyrin-lipid-containing Definity® analogues (pDefs) with >95% efficiency while maintaining microbubble physicochemical properties. Five tri-modal (ultrasound-, positron emission tomography (PET)-, and fluorescent-active) [ 64 Cu]Cu-pDefs are created with varying lipid acyl chain length and charge, representing the most prevalently studied microbubble compositions. In vitro, C16 chain length microbubbles yield 2-3x smaller nanoprogeny than C18 microbubbles post FUS. In vivo, [ 64 Cu]Cu-pDefs are tracked in healthy and 4T1 tumor-bearing mice ± FUS over 48 h qualitatively through fluorescence imaging (to characterize particle disruption) and quantitatively through PET and γ-counting. These studies reveal the impact of microbubble composition and FUS on microbubble dissolution rates, shell circulation, off-target tissue retention (predominantly the liver and spleen), and FUS enhancement of tumor delivery. These findings yield pharmacokinetic microbubble structure-activity relationships that disrupt conventional knowledge, the implications of which on MB-FUS platform design, safety, and nanomedicine delivery are discussed.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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