Multifunctional pathology-mapping theranostic nanoplatforms for US/MR imaging and ultrasound therapy of atherosclerosis
Autor: | Jie Zhou, Huan Zhang, Binyang Gao, Jianbo Huang, Hong Wang, Rui Yang, Yan Luo, Jinshun Xu, Feng Yan |
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Rok vydání: | 2021 |
Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment 02 engineering and technology 030204 cardiovascular system & hematology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo medicine Animals General Materials Science Platelet activation Precision Medicine Scavenger receptor Thrombus Ultrasonography Therapeutic ultrasound business.industry Atherosclerosis 021001 nanoscience & nanotechnology medicine.disease Magnetic Resonance Imaging Plaque Atherosclerotic In vitro PLGA chemistry Microbubbles 0210 nano-technology business |
Zdroj: | Nanoscale. 13:8623-8638 |
ISSN: | 2040-3372 2040-3364 |
Popis: | Atherosclerotic thrombosis is the leading cause of most life-threatening cardiovascular diseases (CVDs), particularly as a result of rupture or erosion of vulnerable plaques. Rupture or erosion-prone plaques are quite different in cellular composition and immunopathology, requiring different treatment strategies. The current imaging technology cannot distinguish the types of vulnerable plaques, and thus empirical treatment is still applied to all without a tailored and precise treatment. Herein, we propose a novel strategy called "Multifunctional Pathology-mapping Theranostic Nanoplatform (MPmTN)" for the tailored treatment of plaques based on the pathological classification. MPmTNs are made up of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), containing contrast imaging materials Fe3O4 and perfluoropentane (PFP), and coated with specific plaque-targeted peptides PP1 and cyclic RGD. The PFP encapsulated inside the MPmTN can undergo a phase change from nanodroplets to gas microbubbles under therapeutic ultrasound (TUS) exposure. The acoustic and biological effects induced by TUS and disruption of microbubbles may further promote therapeutic effects. Hypothetically, MPmTN NPs can target the rupture-prone plaque via the binding of PP1 to class A scavenger receptors (SR-A) on macrophages, induce the apoptosis due to TUS exposure and thus reduce the chronic soakage of inflammatory cells. The MPmTN NPs can also target the erosion-prone plaque through the binding of cRGD to glycoprotein (GP) IIb/IIIa on activated platelets and promote platelet disaggregation under TUS exposure. Therefore, MPmTNs may work as a multifunctional pathology-mapping therapeutic agent. Our in vitro results show that the MPmTN with PP1 and cRGD peptides had a high binding affinity both for activated macrophages and blood clots. Under TUS exposure, the MPmTN could effectively induce macrophage apoptosis, destroy thrombus and exhibit good imaging properties for ultrasound (US) and MRI. In apoE-/- mice, MPmTNs can selectively accumulate at the plaque site and reduce the T2-weighted signal. The apoptosis of macrophages and disaggregation of activated platelets on the plaques were also confirmed in vivo. In summary, this study provides a potential strategy for a tailored treatment of vulnerable plaques based on their pathological nature and a multimodal imaging tool for the risk stratification and assessment of therapeutic efficacy. |
Databáze: | OpenAIRE |
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