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.
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