Scavenger receptor-AI targeted theranostic nanoparticles for regression of atherosclerotic plaques via ABCA1 modulation

IF 4.7 4区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nanomedicine: Nanotechnology, Biology and Medicine Pub Date : 2023-06-01 DOI:10.1016/j.nano.2023.102672

Yan Zhu PhD candidate , Yanni Xu PhD , Dong Han MD, PhD , Xiujin Zhang MD , Cheng Qin MD , Jing Liu BS , Lei Tian MM, MSc , Mengqi Xu PhD candidate , Yan Fang PhD candidate , Yang Zhang MD, PhD , Yabin Wang MD, PhD , Feng Cao MD, PhD

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引用次数: 1

Abstract

ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in atherosclerotic formation through mediated cholesterol efflux in macrophage-derived foam cells. In this study, a scavenger receptors AI (SR-AI) targeted theranostic nanoparticles was constructed for atherosclerosis regression via ABCA1 activation in foam cells. ABCA1-upregulator 5242331 and IR780 were encapsulated in PLGA-PEG micelles which were conjugated with SR-AI targeting peptide (PP1) to formulate the nanoparticles (SAU-NPs). Immunostaining revealed that SR-AI was highly expressed both in macrophage foam cells and in atherosclerotic plaque of ApoE^−/− mice. The SAU-NPs have shown more active targeting to plaque lesion with higher stability compared with non-SR-AI targeted nanoparticles. The transformation from macrophage to foam cells was inhibited by SAU-NPs carried 5242331. Cholesterol deposition was effectively reduced in foam cells by SAU-NPs through activating the LXRα-ABCA1/ABCG1/SR-BI pathway. In conclusion, theranostic SAU-NPs which carried ABCA1-upregulator 5242331 exert beneficial effects on atherosclerosis regression via LXRα activation.

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通过ABCA1调节清除受体- ai靶向治疗纳米颗粒对动脉粥样硬化斑块的消退

atp结合盒转运蛋白A1 (ABCA1)在巨噬细胞源性泡沫细胞中通过介导的胆固醇外溢形成动脉粥样硬化中起关键作用。在本研究中，构建了一种清除受体AI (SR-AI)靶向治疗纳米颗粒，通过在泡沫细胞中激活ABCA1来恢复动脉粥样硬化。将abca1上调因子5242331和IR780包封在PLGA-PEG胶束中，与SR-AI靶向肽(PP1)偶联形成纳米粒子(au - nps)。免疫染色显示，SR-AI在ApoE−/−小鼠巨噬细胞泡沫细胞和动脉粥样硬化斑块中均高表达。与非sr - ai靶向纳米颗粒相比，sa - nps对斑块病变表现出更积极的靶向性，具有更高的稳定性。携带5242331的sa - nps抑制巨噬细胞向泡沫细胞的转化。sa - nps通过激活LXRα-ABCA1/ABCG1/SR-BI通路，有效减少泡沫细胞内胆固醇沉积。综上所述，携带abca1上调因子5242331的治疗性sa - nps通过激活LXRα对动脉粥样硬化的消退具有有益作用。

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来源期刊

Nanomedicine: Nanotechnology, Biology and Medicine 医学-纳米科技

CiteScore

8.10

自引率

3.60%

发文量

104

审稿时长

4.6 months

期刊介绍： Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.