LOCALIZED DELIVERY OF CAVEOLIN-1 PEPTIDE ASSISTED BY ULTRASOUND-MEDIATED MICROBUBBLE DESTRUCTION POTENTIATES THE INHIBITION OF NITRIC OXIDE-DEPENDENT VASODILATION RESPONSE
LOCALIZED DELIVERY OF CAVEOLIN-1 PEPTIDE ASSISTED BY ULTRASOUND-MEDIATED MICROBUBBLE DESTRUCTION POTENTIATES THE INHIBITION OF NITRIC OXIDE-DEPENDENT VASODILATION RESPONSE
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DOI：
10.1016/j.ultrasmedbio.2021.02.003
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发表时间：
2021-04-07
影响因子：
2.9
通讯作者：
Escalante, Bruno
中科院分区：
文献类型：
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作者：
Angel Navarro-Becerra, J.;Franco-Urquijo, Carlos A.;Escalante, Bruno
在内皮中，一氧化氮合酶（eNOS）是产生一氧化氮的酶，一氧化氮是参与多种生物功能和癌症相关事件的关键分子。因此，选择性抑制eNOS代表了NO相关疾病和抗癌治疗的有吸引力的治疗方法。超声介导的微泡破坏（UMMD）结合细胞渗透性肽已被研究作为一种有效的抗癌分子的药物递送系统。我们研究了负载Antennapedia-Caveolin-1肽（AP-Cav），一种特异性的eNOS抑制剂，到微泡的UMD在大鼠主动脉内皮传递的可行性。表征载AP-Cav微泡（AP-Cav-MBs）和US参数。在100-Hz脉冲重复频率、0.5-MPa声压、0.5机械指数和10%占空比下，用UMD处理主动脉30 s，1.3 x 10（8）MBs/mL AP-Cav（8 μ M）-MBs。NO依赖性血管反应使用离体器官系统，治疗后21小时进行评估。在用UMD-AP-Cav-MB处理的动脉瘤中，最大舒张反应被抑制61.8% +/- 1.6%，而在用先前破坏的AP-Cav-MB然后US处理的动脉瘤中，抑制为31.6% +/-1.6%。血管收缩反应不受影响。在用游离AP-Cav处理的拟南芥中评价UMMD的影响;需要30 μ M的游离AP-Cav以达到与用UMMD-AP-Cav-MB获得的抑制反应类似的抑制反应。总之，UMD增强了大鼠主动脉段内皮层中AP-Cav的递送并增强了其作用。(C)2021年世界医学和生物学超声联合会。All rights reserved.
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 x 10(8) MBs/mL AP-Cav (8 mu M)-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 mu M 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. (C) 2021 World Federation for Ultrasound in Medicine & Biology. All rights reserved.