TARGETING OF MACROPHAGE FOAM CELLS IN ATHEROSCLEROTIC PLAQUE USING OLIGONUCLEOTIDE-FUNCTIONALIZED NANOPARTICLES.
TARGETING OF MACROPHAGE FOAM CELLS IN ATHEROSCLEROTIC PLAQUE USING OLIGONUCLEOTIDE-FUNCTIONALIZED NANOPARTICLES.
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DOI：
10.1142/s1793984410000183
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发表时间：
2010-09
期刊：
影响因子：
0.8
通讯作者：
Smith JW
中科院分区：
文献类型：
--
作者：
Sharma G;She ZG;Valenta DT;Stallcup WB;Smith JW
巨噬细胞泡沫细胞是动脉粥样硬化斑块的关键成分，在动脉粥样硬化导致斑块破裂和血栓形成的过程中发挥着重要作用。泡沫细胞正在成为治疗干预和疾病进展成像的有吸引力的目标。因此，设计针对斑块中巨噬细胞泡沫细胞的纳米粒子（NPs）具有相当大的治疗意义。在这里，我们报告了对泡沫细胞具有高亲和力的寡核苷酸功能化纳米粒子系统的构建。用 23 聚鸟嘌呤 (polyG) 寡核苷酸功能化的纳米颗粒可在体外和离体过程中被载脂泡沫细胞上的清道夫受体特异性识别。在乙酰化-LDL（一种已知的清道夫受体配体）的存在下，泡沫细胞对多聚G功能化纳米颗粒的增强摄取受到抑制。由于多聚G寡核苷酸在血清中稳定并且不太可能诱导免疫反应，因此它们用于清道夫受体介导的巨噬细胞泡沫细胞靶向提供了靶向动脉粥样硬化病变的策略。
Macrophage foam cells are key components of atherosclerotic plaque and play an important role in the progression of atherosclerosis leading to plaque rupture and thrombosis. Foam cells are emerging as attractive targets for therapeutic intervention and for imaging the progression of disease. Therefore, designing nanoparticles (NPs) targeted to macrophage foam cells in plaque is of considerable therapeutic significance. Here we report the construction of an oligonucleotide functionalized NP system with high affinity for foam cells. Nanoparticles functionalized with a 23-mer poly-Guanine (polyG) oligonucleotide are specifically recognized by the scavenger receptors on lipid-laden foam cells in vitro and ex vivo. The enhanced uptake of polyG-functionalized NPs by foam cells is inhibited in the presence of acetylated-LDL, a known ligand of scavenger receptors. Since polyG oligonucleotides are stable in serum and are unlikely to induce an immune response, their use for scavenger receptor-mediated targeting of macrophage foam cells provides a strategy for targeting atherosclerotic lesions.