Experimental study on the optimization of ANM33 release in foam cells

Chen Yuan; Liyun Liu; Baihetiya Tayier; Ting Ma; Lina Guan; Yuming Mu; Yanhong Li

doi:10.1515/biol-2022-0564

Experimental study on the optimization of ANM33 release in foam cells

Open Life Sci. 2023 Feb 23;18(1):20220564. doi: 10.1515/biol-2022-0564. eCollection 2023.

Authors

Chen Yuan^{1

2}, Liyun Liu^{1

2}, Baihetiya Tayier^{1

2}, Ting Ma^{1

2}, Lina Guan^{1

2}, Yuming Mu^{1

2}, Yanhong Li^{1

2}

Affiliations

¹ Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China.
² Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, Xinjiang 830011, China.

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.

Keywords: atherosclerosis; drug delivery; dual targeting; foam cells.