Localized Delivery of Caveolin-1 Peptide Assisted by Ultrasound-Mediated Microbubble Destruction Potentiates the Inhibition of Nitric Oxide-Dependent Vasodilation Response
Autor: | J. Angel Navarro-Becerra, Bruno Escalante, Amelia Rios, Carlos A. Franco-Urquijo |
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Rok vydání: | 2020 |
Předmět: |
Male
Acoustics and Ultrasonics Endothelium Caveolin 1 Biophysics Vasodilation 030204 cardiovascular system & hematology Pharmacology Nitric Oxide 01 natural sciences Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Enos 0103 physical sciences medicine Animals Radiology Nuclear Medicine and imaging Rats Wistar Ultrasonography Microbubbles 010304 chemical physics Radiological and Ultrasound Technology biology biology.organism_classification Rats Nitric oxide synthase medicine.anatomical_structure chemistry Drug delivery cardiovascular system biology.protein Nitric Oxide Synthase |
Zdroj: | Ultrasound in medicinebiology. 47(6) |
ISSN: | 1879-291X |
Popis: | In the endothelium, nitric oxide synthase (eNOS) is the enzyme that generates nitric oxide, a key molecule involved in a variety of biological functions and cancer-related events. Therefore, selective inhibition of eNOS represents an attractive therapeutic approach for NO-related diseases and anticancer therapy. Ultrasound-mediated microbubble destruction (UMMD) conjugated with cell-permeable peptides has been investigated as a drug delivery system for effective delivery of anticancer molecules. We investigated the feasibility of loading antennapedia-caveolin-1 peptide (AP-Cav), a specific eNOS inhibitor, onto microbubbles to be delivered by UMMD in rat aortic endothelium. AP-Cav-loaded microbubbles (AP-Cav-MBs) and US parameters were characterized. Aortas were treated with UMMD for 30 s with 1.3 × 108 MBs/mL AP-Cav (8 μM)-MBs at 100-Hz pulse repetition frequency, 0.5-MPa acoustic pressure, 0.5 mechanical index and 10% duty cycle. NO-dependent vascular responses were assessed using an isolated organ system, 21 h post-treatment. Maximal relaxation response was inhibited 61.8% ± 1.6% in aortas treated with UMMD-AP-Cav-MBs, while in aortas treated with previously disrupted AP-Cav-MBs and then US, the inhibition was 31.6% ± 1.6%. The vascular contractile response was not affected. The impact of UMMD was evaluated in aortas treated with free AP-Cav; 30 μM of free AP-Cav was necessary to reach an inhibition response similar to that obtained with UMMD-AP-Cav-MBs. In conclusion, UMMD enhances the delivery and potentiates the effect of AP-Cav in the endothelial layer of rat aorta segments. |
Databáze: | OpenAIRE |
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