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Abstract：
Given the miR-33\'s mechanistic relationships with multiple etiological factors in the pathogenesis of atherosclerosis (AS), we investigated the therapeutic potentials of dual-targeted microbubbles (HA-PANBs) in foam cell-specific release of anti-miR-33 (ANM33) oligonucleotides, resulting in the early prevention of AS progression and severity. The intracellular localization, loading optimization, and therapeutic effects of HA-PANBs were examined in detail in a co-cultured cell model of phagocytosis. Compared with non-targeting nanobubbles (NBs) and single-targeted microbubbles as controls, HA-PANBs efficiently delivered the ANM33 specifically to foam cells via sustained release, exhibiting its clinical value in mediating RNA silencing. Moreover, when used at a dose of 12 µg/mL HA-PANBs per 107 cells for 48 h, a higher release rate and drug efficacy were observed. Therefore, HA-PANBs, effectively targeting early AS foam cells, may represent a novel and optimal gene therapy approach for AS management.
摘要：
鉴于miR-33在动脉粥样硬化（AS）的发病机制中与多种病因因素的机制关系，我们研究了双靶向微泡（HA-PANBs）在抗miR-33（ANM33）寡核苷酸的泡沫细胞特异性释放中的治疗潜力，导致早期预防AS进展和严重程度。细胞内定位，加载优化，在吞噬作用的共培养细胞模型中详细检查了HA-PANBs的治疗效果。与非靶向纳米气泡（NBs）和单靶向微泡作为对照相比，HA-PANB通过持续释放有效地将ANM33特定地递送至泡沫细胞，在介导RNA沉默方面表现出其临床价值。此外，当以每107个细胞12微克/毫升HA-PANBs的剂量使用48小时时，观察到更高的释放速率和药物疗效。因此,HA-PANB,有效靶向早期AS泡沫细胞，可能代表了一种新的和最佳的基因治疗方法用于AS管理。
