Localized Delivery of Caveolin-1 Peptide Assisted by Ultrasound-Mediated Microbubble Destruction Potentiates the Inhibition of Nitric Oxide-Dependent Vasodilation Response

J. Angel Navarro-Becerra, Carlos A. Franco-Urquijo, Amelia Ríos, Bruno Alfonso Escalante Acosta

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1559-1572
Number of pages14
JournalUltrasound in Medicine and Biology
Volume47
Issue number6
DOIs
Publication statusPublished - Jun 2021

Bibliographical note

Funding Information:
This work was supported by the Mexican Council for Science and Technology (CONACyT, Grant 1180 to BE). JANB and CAFU are fellows from CONACyT. The authors declare that there are no conflicts of interest regarding the publication of this article.

Publisher Copyright:
© 2021 World Federation for Ultrasound in Medicine & Biology

All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology
  • Biophysics
  • Acoustics and Ultrasonics

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