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

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 

作者机构：Department of RadiologySecond Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China Materdicine LabSchool of Life SciencesShanghai UniversityShanghai200444PR China Chongqing Key Laboratory of Ultrasound Molecular Imaging&Department of UltrasoundSecond Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China State Key Laboratory of High Performance Ceramics and Superfine MicrostructureShanghai Institute of CeramicsChinese Academy of SciencesShanghai200050PR China Department of RadiologyChildren’s Hospital of Chongqing Medical UniversityChongqing400014PR China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2022年第7卷第10期

页      面：120-133页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 

基　　金：support from the National Natural Science Foundation of China(Grant Nos.81701650,81971608,and 82172092) the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University(Grant No.2020-7) the Science&Technology Commission Foundation of Chongqing(Grant No.cstc2017jcyjAX0444). 

主　　题：Vulnerable plaques Acoustic droplet vaporization Macrophages Apoptosis Nanomedicine 

摘      要：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.