Transferrin Receptor-Targeted Nonspherical Microbubbles for Blood-Brain Barrier Sonopermeation.

Autor: Dasgupta A; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany.; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, 02134, USA., Sun T; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, 02134, USA.; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Rama E; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., Motta A; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., Zhang Y; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Power C; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Moeckel D; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., Fletcher SM; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Moosavifar M; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., Barmin R; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., Porte C; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., Buhl EM; Electron Microscopy Facility, Institute of Pathology, RWTH Aachen University, 52074, Aachen, Germany., Bastard C; DWI - Leibniz Institute for Interactive Materials, RWTH Aachen University Hospital, 52074, Aachen, Germany., Pallares RM; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., Kiessling F; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany., McDannold N; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Mitragotri S; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, 02134, USA., Lammers T; Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2023 Dec; Vol. 35 (52), pp. e2308150. Date of Electronic Publication: 2023 Nov 27.
DOI: 10.1002/adma.202308150
Abstrakt: Microbubbles (MB) are widely used for ultrasound (US) imaging and drug delivery. MB are typically spherically shaped, due to surface tension. When heated above their glass transition temperature, polymer-based MB can be mechanically stretched to obtain an anisotropic shape, endowing them with unique features for US-mediated blood-brain barrier (BBB) permeation. It is here shown that nonspherical MB can be surface-modified with BBB-specific targeting ligands, thereby promoting binding to and sonopermeation of blood vessels in the brain. Actively targeted rod-shaped MB are generated via 1D stretching of spherical poly(butyl cyanoacrylate) MB and via subsequently functionalizing their shell with antitransferrin receptor (TfR) antibodies. Using US and optical imaging, it is demonstrated that nonspherical anti-TfR-MB bind more efficiently to BBB endothelium than spherical anti-TfR-MB, both in vitro and in vivo. BBB-associated anisotropic MB produce stronger cavitation signals and markedly enhance BBB permeation and delivery of a model drug as compared to spherical BBB-targeted MB. These findings exemplify the potential of antibody-modified nonspherical MB for targeted and triggered drug delivery to the brain.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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