An in vitro study on the feasibility of precise intracellular drug release from dual-targeted lipid ultrasound microbubbles loaded with ANM33
10.3760/cma.j.cn131148-20240117-00041
- VernacularTitle:载ANM33双靶标脂质超声微泡精准胞内释药可行性的体外研究
- Author:
Ruining LIU
1
;
Shangke CHEN
;
Tayier BAIHETIYA·
;
Lina GUAN
;
Yuming MU
Author Information
1. 新疆医科大学第一附属医院心脏超声诊断科，乌鲁木齐 830000
- Keywords:
Atherosclerosis;
Dual-targeted lipid ultrasound microbubbles loaded with ANM33;
Macrophages;
Precise drug release
- From:
Chinese Journal of Ultrasonography
2024;33(7):617-625
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare dual-targeted lipid ultrasound microbubbles loaded with ANM33 (HA-PANBs) and evaluate its feasibility in targeting foam cells by stages and achieving precise intracellular drug release in vitro. Methods:The dual-targeteded lipid ultrasound microbubbles were designed with nanobubbles (NBs) as the microbubble core, hyaluronic acid (HA) as the first-stage targeting ligand for damaged endothelial cells, aptamer PM1 as the second-stage targeting moiety for foam cells, and ANM33 as the therapeutic factor. Simultaneously with the characterization of the lipid bubbles, the stability and in vitro contrast-enhanced ultrasound imaging capability were detected. Then a co-culture model of damaged human umbilical vein endothelial cells (HUVEC) and macrophages (RAW264.7, MΦ) was established, combined with flow cytometry, oil red O staining and small animal in vivo imaging to evaluate the ability of HA-PANBs in targeting foam cells precisely and releasing ANM33. Results:The HA-PANBs exhibited regular morphology and good structural stability, with a particle size of (1 357.53±140.20)nm and a surface potential of (-5.61±0.73)mV. HA, PM1 and ANM33 were effectively connected. In the damaged HUVEC/MΦ co-culture system, the HA-PANBs group demonstrated the best targeting effect on foam cells, with an effective uptake of (80.65±2.12)%, which was 56.74% higher than that of the NBs group. Oil red O staining revealed that the cholesterol efflux capacity of foam cells in the HA-PANBs group was significantly better than that in the NBs group, the results were statistically different [(629.80±21.99) a.u.vs (1 071.00±55.49)a.u., P<0.05]. Conclusions:The dual-targeted lipid ultrasound microbubbles (HA-PANBs) can precisely target foam cells and significantly enhance their cholesterol efflux, providing a new strategy for the early non-invasive diagnosis and treatment of atherosclerosis.
