An Ultrasound-Responsive Theranostic Cyclodextrin-Loaded Nanoparticle for Multimodal Imaging and Therapy for Atherosclerosis,Small

当前位置： X-MOL 学术 › Small › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

An Ultrasound-Responsive Theranostic Cyclodextrin-Loaded Nanoparticle for Multimodal Imaging and Therapy for Atherosclerosis
Small ( IF 13.0 ) Pub Date : 2022-06-16 , DOI: 10.1002/smll.202200967
Sourabh Mehta _{1,

2,

3,

4} , Viktoria Bongcaron _{1,

5} , Tien K Nguyen ₆ , Yugandhara Jirwanka ₇ , Ana Maluenda ₁ , Aidan P G Walsh _{1,

4,

5} , Jathushan Palasubramaniam _{1,

4,

5} , Mark D Hulett ₆ , Rohit Srivastava _{2,

3} , Alex Bobik _{8,

9} , Xiaowei Wang _{1,

4,

5,

10,

11} , Karlheinz Peter _{1,

4,

8,

10,

11}

Affiliation

Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, 400076, India.
Indian Institute of Technology Bombay - Monash Research Academy, Powai, 400076, India.
Department of Medicine, Monash University, Melbourne, VIC, 3004, Australia.
Molecular Imaging and Theranostics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.
Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University Melbourne, Melbourne, VIC, 3083, Australia.
Toxicology Division, National Institute for Research in Reproductive and Child Health, Parel, 400012, India.
Department of Immunology, Monash University, Melbourne, VIC, 3004, Australia.
Vascular Biology and Atherosclerosis Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.
Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, 3083, Australia.
Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, 3052, Australia.

Atherosclerosis is a major cause of mortality and morbidity worldwide. Left undiagnosed and untreated, atherosclerotic plaques can rupture and cause cardiovascular complications such as myocardial infarction and stroke. Atherosclerotic plaques are composed of lipids, including oxidized low-density lipoproteins and cholesterol crystals, and immune cells, including macrophages. 2-Hydroxypropyl-beta-cyclodextrin (CD) is FDA-approved for capturing, solubilizing, and delivering lipophilic drugs in humans. It is also known to dissolve cholesterol crystals and decrease atherosclerotic plaque size. However, its low retention time necessitates high dosages for successful therapy. This study reports CD delivery via air-trapped polybutylcyanoacrylate nanoparticles (with diameters of 388 ± 34 nm) loaded with CD (CDNPs). The multimodal contrast ability of these nanoparticles after being loaded with IR780 dye in mice is demonstrated using ultrasound and near-infrared imaging. It is shown that CDNPs enhance the cellular uptake of CD in murine cells. In an ApoE^–/– mouse model of atherosclerosis, treatment with CDNPs significantly improves the anti-atherosclerotic efficacy of CD. Ultrasound triggering further improves CD uptake, highlighting that CDNPs can be used for ultrasound imaging and ultrasound-responsive CD delivery. Thus, CDNPs represent a theranostic nanocarrier for potential application in patients with atherosclerosis.

中文翻译：

用于动脉粥样硬化多模式成像和治疗的超声响应治疗诊断环糊精纳米颗粒

动脉粥样硬化是全世界死亡率和发病率的主要原因。未经诊断和治疗，动脉粥样硬化斑块会破裂并导致心血管并发症，例如心肌梗塞和中风。动脉粥样硬化斑块由脂质（包括氧化的低密度脂蛋白和胆固醇晶体）和免疫细胞（包括巨噬细胞）组成。2-羟丙基-β-环糊精 (CD) 经 FDA 批准用于在人体中捕获、溶解和输送亲脂性药物。它还可以溶解胆固醇晶体并减少动脉粥样硬化斑块的大小。然而，它的低保留时间需要高剂量才能成功治疗。本研究报告通过载有 CD (CDNPs) 的空气捕获的聚氰基丙烯酸丁酯纳米粒子（直径为 388 ± 34 nm）进行 CD 递送。使用超声和近红外成像证明了这些纳米颗粒在小鼠中加载 IR780 染料后的多模态对比能力。结果表明，CDNPs 增强了鼠细胞中 CD 的细胞摄取。在 ApoE 中^–/–动脉粥样硬化小鼠模型，CDNPs 治疗显着提高了 CD 的抗动脉粥样硬化功效。超声触发进一步提高了 CD 吸收，突出表明 CDNP 可用于超声成像和超声响应 CD 输送。因此，CDNPs 代表了一种潜在应用于动脉粥样硬化患者的治疗诊断纳米载体。

更新日期：2022-06-16

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11