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

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posted on 2022-09-01, 08:15 authored by S Mehta, V Bongcaron, Tien NguyenTien Nguyen, Y Jirwanka, A Maluenda, APG Walsh, J Palasubramaniam, Mark HulettMark Hulett, R Srivastava, A Bobik, Xiaowei WangXiaowei Wang, Karlheinz PeterKarlheinz Peter
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.


X.W. and K.P. contributed equally to this work. The authors wish to acknowledge the Industrial Research and Consultancy Centre and Sophisticated Analytical Instruments Facility at the IIT Bombay for providing access to their microscopy facility. Some figures were created with BioRender. S.M. would like to acknowledge the Department of Biotechnology, Government of India, for sponsoring his Ph.D. scholarship. A.P.G.W. and J.P. are supported by Monash University Scholarships. J.P. is also supported by a National Health and Medical Research Council (NHMRC) of Australia Postgraduate Scholarship. Y.J. is supported by a Ph.D. scholarship from the Department of Biotechnology, Government of India. X.W. is supported by a Future Leader Fellowship from the National Heart Foundation of Australia and the Baker Fellowship. K.P. is supported by an L3 Investigator Fellowship from the NHMRC.Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians.


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© 2022 The Authors. Small published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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