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LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques

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Bioactive Materials 2022年第10期7卷 120-133页

作者： Jingxin Hou Jun Zhou Meiqi Chang Guangcheng Bao Jie Xu Man Ye Yixin Zhong Shuling Liu Junrui Wang Wei Zhang Haitao Ran Zhigang Wang Yu Chen Dajing Guo Department of Radiology Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China Materdicine Lab School of Life SciencesShanghai UniversityShanghai200444PR China Chongqing Key Laboratory of Ultrasound Molecular Imaging&Department of Ultrasound Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050PR China Department of Radiology Children’s Hospital of Chongqing Medical UniversityChongqing400014PR China

Due to the high risk of tearing and rupture,vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases.Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event,but the efficiency is still low and undesirable.Herein,we rationally design and engineer the low-intensity focused ultrasound(LIFU)-responsive FPD@CD nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane(PFH)into biocompatible PLGA-PEG-PLGA nanoparticles(PPP NPs)and then attaching dextran sulphate(DS)onto the surface of PPP NPs for targeting delivery.DS,as a typical macrophages-targeted molecule,can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization(ADV)effect.In addition,the introduction of DiR and Fe3O4 endows nanomedicine with near-infrared fluorescence(NIRF)and magnetic resonance(MR)imaging capabilities.The engineered FPD@CD nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes.A reduction of 49.4%of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period.This specific,efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.

关键词： Vulnerable plaques acoustic droplet vaporization Macrophages Apoptosis Nanomedicine

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