Photothermal Therapy Based on CuS Nanoparticles for Alleviating Arterial Restenosis Induced by Mechanical Injury of Endovascular Treatment

Xiaoyu Wu,Xinrui Yang,Qin Zhang,Ruihua Wang,Qun Huang,Kun Liu,Xiaobing Liu

doi:10.3389/fmats.2020.591281

Abstract

CuS nanoparticles (NPs) as an effective near-infrared absorption agent have been widely applied in the photothermal therapy (PTT) of cancer. However, little is known about the application of CuS NP-based PTT in alleviating arterial inflammation and restenosis, which affects the long-term prognosis of endovascular treatment. In this study, CuS NPs were synthesized and used as PTT nanoplatform for ameliorating arterial inflammation induced by mechanical injury of endovascular treatment. The macrophages possess powerful phagocytosis toward CuS NPs is evidenced by intracellular transmission electron microscopic imaging. As illustrated from Cell Counting Kit-8 assay and calcein AM/PI staining, an efficient depletion of macrophages by CuS NPs coculture combined with the irradiation with a 915-nm near-infrared laser was achieved. The endarterium injury/inflammation model was established by insertion of a 29G needle (BD Insulin Syringe Ultra-Fine®) to the left common carotid artery of an apolipoprotein E knockout mouse to mimic endarterium damage after endovascular treatment. Local injection of CuS NPs around the left common carotid artery followed by irradiation with a 915-nm INR laser significantly depleted infiltrated macrophages and alleviated arterial stenosis. This work emphasizes the role of CuS NPs as a PTT agent in post-injury remodeling of the arterial wall and provides an attractive target macrophage that can be depleted to alleviate arterial restenosis.

Highlights

Atherosclerosis obliterans of the extracranial carotid artery accounts for 15–20% of ischemic strokes (Li et al, 2015)
To detect the possibility of applying photothermal therapy (PTT) using CuS NPs in ablating macrophages, we evaluated the phagocytosis of macrophages toward the CuS NPs using transmission electron microscope (TEM)
Nontoxic and biocompatible CuS NPs can be engulfed by macrophages so that efficient photothermal depletion of macrophages was achieved in vitro and in vivo

Summary

Introduction

Atherosclerosis obliterans of the extracranial carotid artery accounts for 15–20% of ischemic strokes (Li et al, 2015). Regardless of refinements of the endovascular technique, the mechanical injury to the endarterium is unavoidable, and subsequent arterial inflammation and restenosis are still incompletely understood and entirely unpredictable or unpreventable (Hong and Lee, 2020). Photothermal Treatment endothelial cells, neutrophils, and platelets (Arakawa et al, 2005) and recruits massive circulating monocytes to the arterial intima (Koelwyn et al, 2018). Via serious signaling pathways (Tong et al, 2020), recruited monocytes differentiate into macrophages, which mediates the chronic inflammation of the injured artery (Koelwyn et al, 2018). Depletion of abnormal infiltrated macrophages provides novel insights into alleviating restenosis after endovascular treatment

Methods

Results

Conclusion