دورية أكاديمية
أعرض في EDS

Targeted opening of the blood-brain barrier using VCAM-1 functionalised microbubbles and "whole brain" ultrasound.

التفاصيل البيبلوغرافية
العنوان: Targeted opening of the blood-brain barrier using VCAM-1 functionalised microbubbles and "whole brain" ultrasound.
المؤلفون: Johanssen VA; Department of Oncology, University of Oxford, Oxford, UK., Ruan JL; Department of Oncology, University of Oxford, Oxford, UK., Vince O; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK., Thomas A; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK., Peeters S; Department of Oncology, University of Oxford, Oxford, UK., Soto MS; Department of Oncology, University of Oxford, Oxford, UK., Buck J; Department of Oncology, University of Oxford, Oxford, UK., Gray M; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK., Stride E; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK.; Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Research, University of Oxford, UK., Sibson NR; Department of Oncology, University of Oxford, Oxford, UK.
المصدر: Theranostics [Theranostics] 2024 Jul 02; Vol. 14 (10), pp. 4076-4089. Date of Electronic Publication: 2024 Jul 02 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-
مواضيع طبية MeSH: Blood-Brain Barrier*/metabolism , Blood-Brain Barrier*/diagnostic imaging , Microbubbles* , Brain Neoplasms*/diagnostic imaging , Vascular Cell Adhesion Molecule-1*/metabolism , Magnetic Resonance Imaging*/methods, Animals ; Mice ; Contrast Media ; Brain/diagnostic imaging ; Brain/metabolism ; Female ; Disease Models, Animal ; Ultrasonography/methods ; Cell Line, Tumor ; Gadolinium DTPA/administration & dosage ; Humans ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/pathology ; Breast Neoplasms/metabolism
مستخلص: Metastatic tumours in the brain now represent one of the leading causes of death from cancer. Current treatments are largely ineffective owing to the combination of late diagnosis and poor delivery of therapies across the blood-brain barrier (BBB). Conjugating magnetic resonance imaging (MRI) contrast agents with a monoclonal antibody for VCAM-1 (anti-VCAM1) has been shown to enable detection of micrometastases, two to three orders of magnitude smaller in volume than those currently detectable clinically. The aim of this study was to exploit this targeting approach to enable localised and temporary BBB opening at the site of early-stage metastases using functionalised microbubbles and ultrasound. Methods: Microbubbles functionalised with anti-VCAM1 were synthesised and shown to bind to VCAM-1-expressing cells in vitro . Experiments were then conducted in vivo in a unilateral breast cancer brain metastasis mouse model using Gadolinium-DTPA (Gd-DTPA) enhanced MRI to detect BBB opening. Following injection of Gd-DTPA and targeted microbubbles, the whole brain volume was simultaneously exposed to ultrasound (0.5 MHz, 10% duty cycle, 0.7 MPa peak negative pressure, 2 min treatment time). T1-weighted MRI was then performed to identify BBB opening, followed by histological confirmation via immunoglobulin G (IgG) immunohistochemistry. Results: In mice treated with targeted microbubbles and ultrasound, statistically significantly greater extravasation of Gd-DTPA and IgG was observed in the left tumour-bearing hemisphere compared to the right hemisphere 5 min after treatment. No acute adverse effects were observed. There was no investigation of longer term bioeffects owing to the nature of the study. Conclusion: The results demonstrate the feasibility of using targeted microbubbles in combination with low intensity ultrasound to localise opening of the BBB to metastatic sites in the brain. This approach has potential application in the treatment of metastatic tumours whose location cannot be established a priori with conventional imaging methods.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)
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فهرسة مساهمة: Keywords: blood-brain barrier; metastases; microbubbles; targeted drug delivery; therapeutic ultrasound
المشرفين على المادة: 0 (Vascular Cell Adhesion Molecule-1)
0 (Contrast Media)
K2I13DR72L (Gadolinium DTPA)
تواريخ الأحداث: Date Created: 20240712 Date Completed: 20240712 Latest Revision: 20240718
رمز التحديث: 20240718
مُعرف محوري في PubMed: PMC11234285
DOI: 10.7150/thno.93172
PMID: 38994029
قاعدة البيانات: MEDLINE
الوصف
تدمد:1838-7640
DOI:10.7150/thno.93172