Osteopontin targeted theranostic nanoprobes for laser-induced synergistic regression of vulnerable atherosclerotic plaques  

作　　者：Mengqi Xu Cong Mao Haoting Chen Lu Liu Yabin Wang Abid Hussain Sulei Li Xu Zhang Ruslan G.Tuguntaev Xing-Jie Liang Weisheng Guo Feng Cao 

机构地区：[1]Department of Cardiology,National Clinical Research Center for Geriatric Diseases&Second Medical Center of Chinese PLA General Hospital,Beijing 100853,China [2]Department of Minimally Invasive Interventional Radiology,Key Laboratory of Molecular Target&Clinical Pharmacology,School of Pharmaceutical Sciences&the Second Affiliated Hospital,Guangzhou Medical University,Guangzhou 510260,China [3]Laboratory of Controllable Nanopharmaceuticals,Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety,National Center for Nanoscience and Technology,Beijing 100190,China [4]Department of Urology,Chinese PLA General Hospital,Beijing 100853,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第4期2014-2028,共15页药学学报（英文版）

基　　金：This work was supported by the National Nature Science Foundation of China(Nos.81820108019,91939303 and 31971302);the National Key Research and Development Program of China(2018YFC0116305);the Science Foundation of PLA General Hospital(2018XXFC-9,CX19028,China).

摘　　要：Vulnerable atherosclerotic plaque(VASPs)is the major pathological cause of acute cardiovascular event.Early detection and precise intervention of VASP hold great clinical significance,yet remain a major challenge.Photodynamic therapy(PDT)realizes potent ablation efficacy under precise manipulation of laser irradiation.In this study,we constructed theranostic nanoprobes(NPs),which could precisely regress VASPs through a cascade of synergistic events triggered by local irradiation of lasers under the guidance of fluorescence/MR imaging.The NPs were formulated from human serum albumin(HSA)conjugated with a high affinity-peptide targeting osteopontin(OPN)and encapsulated with photosensitizer IR780 and hypoxia-activatable tirapazamine(TPZ).After intravenous injection into atherosclerotic mice,the OPN-targeted NPs demonstrated high specific accumulation in VASPs due to the overexpression of OPN in activated foamy macrophages in the carotid artery.Under the visible guidance of fluorescence and MR dual-model imaging,the precise near-infrared(NIR)laser irradiation generated massive reactive oxygen species(ROS),which resulted in efficient plaque ablation and amplified hypoxia within VASPs.In response to the elevated hypoxia,the initially inactive TPZ was successively boosted to present potent biological suppression of foamy macrophages.After therapeutic administration of the NPs for 2 weeks,the plaque area and the degree of carotid artery stenosis were markedly reduced.Furthermore,the formulated NPs displayed excellent biocompatibility.In conclusion,the developed HSA-based NPs demonstrated appreciable specific identification ability of VASPs and realized precise synergistic regression of atherosclerosis.

关 键 词：Vulnerable atherosclerotic plaques Theranostic nanoprobe Human serum albumin OSTEOPONTIN Photodynamic therapy Hypoxia Reactive oxygen species TIRAPAZAMINE 

分 类 号：R543.5[医药卫生—心血管疾病]