دورية أكاديمية
أعرض في EDS

Potentiation of anti-angiogenic eNOS-siRNA transfection by ultrasound-mediated microbubble destruction in ex vivo rat aortic rings.

التفاصيل البيبلوغرافية
العنوان: Potentiation of anti-angiogenic eNOS-siRNA transfection by ultrasound-mediated microbubble destruction in ex vivo rat aortic rings.
المؤلفون: Villa-Martínez E; Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Apodaca, Nuevo León, México., Rios A; Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Apodaca, Nuevo León, México., Gutiérrez-Vidal R; Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Apodaca, Nuevo León, México.; Programa de Investigadoras e Investigadores por México, CONAHCyT/Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Apodaca, Nuevo León, México., Escalante B; Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Apodaca, Nuevo León, México.
المصدر: PloS one [PLoS One] 2024 Aug 01; Vol. 19 (8), pp. e0308075. Date of Electronic Publication: 2024 Aug 01 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Nitric Oxide Synthase Type III*/metabolism , Nitric Oxide Synthase Type III*/genetics , RNA, Small Interfering*/genetics , RNA, Small Interfering*/metabolism , Microbubbles* , Transfection*/methods , Aorta*/metabolism , Nitric Oxide*/metabolism, Animals ; Rats ; Mice ; Male ; Cell Line ; Neovascularization, Physiologic/genetics
مستخلص: Nitric oxide (NO) regulates vascular homeostasis and plays a key role in revascularization and angiogenesis. The endothelial nitric oxide synthase (eNOS) enzyme catalyzes NO production in endothelial cells. Overexpression of the eNOS gene has been implicated in pathologies with dysfunctional angiogenic processes, such as cancer. Therefore, modulating eNOS gene expression using small interfering RNAs (siRNAs) represents a viable strategy for antitumor therapy. siRNAs are highly specific to the target gene, thus reducing off-target effects. Given the widespread distribution of endothelium and the crucial physiological role of eNOS, localized delivery of nucleic acid to the affected area is essential. Therefore, the development of an efficient eNOS-siRNA delivery carrier capable of controlled release is imperative for targeting specific vascular regions, particularly those associated with tumor vascular growth. Thus, this study aims to utilize ultrasound-mediated microbubble destruction (UMMD) technology with cationic microbubbles loaded with eNOS-siRNA to enhance transfection efficiency and improve siRNA delivery, thereby preventing sprouting angiogenesis. The efficiency of eNOS-siRNA transfection facilitated by UMMD was assessed using bEnd.3 cells. Synthesis of nitric oxide and eNOS protein expression were also evaluated. The silencing of eNOS gene in a model of angiogenesis was assayed using the rat aortic ring assay. The results showed that from 6 to 24 h, the transfection of fluorescent siRNA with UMMD was twice as high as that of lipofection. Moreover, transfection of eNOS-siRNA with UMMD enhanced the knockdown level (65.40 ± 4.50%) compared to lipofectamine (40 ± 1.70%). Silencing of eNOS gene with UMMD required less amount of eNOS-siRNA (42 ng) to decrease the level of eNOS protein expression (52.30 ± 0.08%) to the same extent as 79 ng of eNOS-siRNA using lipofectamine (56.30 ± 0.10%). NO production assisted by UMMD was reduced by 81% compared to 67% reduction transfecting with lipofectamine. This diminished NO production led to higher attenuation of aortic ring outgrowth. Three-fold reduction compared to lipofectamine transfection. In conclusion, we propose the combination of eNOS-siRNA and UMMD as an efficient, safe, non-viral nucleic acid transfection strategy for inhibition of tumor progression.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Villa-Martínez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: EC 1.14.13.39 (Nitric Oxide Synthase Type III)
0 (RNA, Small Interfering)
31C4KY9ESH (Nitric Oxide)
تواريخ الأحداث: Date Created: 20240801 Date Completed: 20240801 Latest Revision: 20240803
رمز التحديث: 20240803
مُعرف محوري في PubMed: PMC11293687
DOI: 10.1371/journal.pone.0308075
PMID: 39088581
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0308075