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

Bioactive Materials

Zhigang Wang¹  Dajing Guo¹  Yu Chen²  Haitao Ran²  Guangcheng Bao³  Jingxin Hou⁴  Wei Zhang⁴  Jun Zhou⁴  Jie Xu⁴  Shuling Liu⁴  Junrui Wang⁴  Yixin Zhong⁴  Man Ye⁴  Meiqi Chang⁵ 

[1] Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China;;Chongqing Key Laboratory of Ultrasound Molecular Imaging &Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China;Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China;State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, PR China;

关键词: Vulnerable plaques;    Acoustic droplet vaporization;    Macrophages;    Apoptosis;    Nanomedicine;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown