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

引用

Acta Pharmaceutica Sinica B 2022年第4期12卷 2014-2028页

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 Department of Cardiology National Clinical Research Center for Geriatric Diseases&Second Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Minimally Invasive Interventional Radiology Key Laboratory of Molecular Target&Clinical PharmacologySchool of Pharmaceutical Sciences&the Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Laboratory of Controllable Nanopharmaceuticals Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China Department of Urology Chinese PLA General HospitalBeijing 100853China

vulnerable atherosclerotic plaque(VASPs)is the major pathological cause of acute cardiovascular *** detection and precise intervention of VASP hold great clinical significance,yet remain a major *** therapy(PDT)realizes potent ablation efficacy under precise manipulation of laser *** 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 *** 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 *** 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 *** response to the elevated hypoxia,the initially inactive TPZ was successively boosted to present potent biological suppression of foamy *** therapeutic administration of the NPs for 2 weeks,the plaque area and the degree of carotid artery stenosis were markedly ***,the formulated NPs displayed excellent *** 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

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