LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques
Jingxin Hou, Jun Zhou, Meiqi Chang, Guangcheng Bao, Jie Xu, Man Ye, Yixin Zhong, Shilin Liu, Junrui Wang, Wei Zhang, Haitao Ran, Zhigang Wang, Yu Chen, Dajing Guo
Abstract
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 [email protected] 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 [email protected] 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.