Applications of inorganic nanoparticles in the diagnosis and therapy of atherosclerosis

Dai, Ting; He, Wenming; Yao, Changliang; Ma, Xuehua; Ren, Wenzhi; Mai, Yifeng; Wu, Aiguo

doi:10.1039/d0bm00196a

Cited by 61 publications

(33 citation statements)

References 120 publications

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“…Traditional drug therapies including lipid-lowering drugs (e.g., statins, fibrates), platelet aggregation inhibitors, antihypertensive drugs, and anti-diabetic drugs (e.g., thiazolidinediones) generally suffer from low therapeutic efficacy and severe side effects, necessitating the development of novel drug carriers for precise AS treatment [3]. Consequently, a variety of organic or inorganic nanoparticles have emerged to combat AS by engineering nanoagents with versatile functionalization [4,5].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid-Functionalized Mesoporous Silica Nanoparticles Loading Simvastatin for Targeted Therapy of Atherosclerosis

et al. 2022

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Atherosclerosis (AS) constitutes a major threat to human health, yet most current therapeutics are hindered in achieving desirable clinical outcomes by low bioavailability or serious side effects. Herein, we constructed an enzyme-responsive and macrophage-targeting drug delivery system (SIM@HA-MSN) which can potentially modulate the microenvironment of the atherosclerotic plaques characterized by excessive inflammation and overexpression of hyaluronidase (HAase) for precise AS treatment. More specifically, mesoporous silica nanoparticles (MSNs) were loaded with a lipid-lowering drug simvastatin (SIM) and further gated with hyaluronic acid (HA) coating, which endowed the nanosystem with HAase responsiveness and targetability to inflammatory macrophages. Our results showed that a high loading efficiency (>20%) and excellent enzyme-responsive release of SIM were simultaneously achieved for the first time by silica-based nanocarriers through formulation optimizations. Moreover, in vitro experiments confirmed that SIM@HA-MSN possessed robust targeting, anti-inflammatory, and anti-foaming effects, along with low cytotoxicity and excellent hemocompatibility. In addition, preliminary animal experiments demonstrated the as-established nanosystem had a long plasma-retention time and good biocompatibility in vivo. Taken together, SIM@HA-MSN with HA playing triple roles including gatekeeping, lesion-targeting, and long-circulating holds great potential for the management of atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid-Functionalized Mesoporous Silica Nanoparticles Loading Simvastatin for Targeted Therapy of Atherosclerosis

et al. 2022

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“…have been widely used in the diagnosis and therapy of atherosclerosis. [ 14 ] To date, antiangiogenic drugs and vascular endothelial growth factor‐A (VEGF‐A) blockers constitute the central therapeutic axis to suppress plaque neovascularization. However, antiangiogenic drugs display non‐negligible systemic toxicity, whereas systemic use of VEGF‐A inhibitors promotes significant hypertensive and thromboembolic events.…”

Section: Introductionmentioning

confidence: 99%

Low‐Intensity Focused Ultrasound‐Responsive Ferrite‐Encapsulated Nanoparticles for Atherosclerotic Plaque Neovascularization Theranostics

et al. 2021

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Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging-guided SDT in plaque angiogenesis theranostics, termed PFP-HMME@PLGA/ MnFe 2 O 4 -ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe 2 O 4 ), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid-glycolic acid (PLGA) shells and is conjugated to an anti-VEGFR-2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP-mediated SDT promotes mitochondrial-caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP-mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP-mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP-mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.

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“…Atherosclerosis has been recognized as a progressive chronic inflammatory disease, featured by the formation of atheromatous plaques in the subendothelial layer of artery wall. − A ruptured plaque may induce thrombosis and obstruction in arteries, inducing major clinical consequences. − The conventional interventions for preventing the progression of atherosclerotic plaques include life style changes and appropriate medications, − such as oral administration of statins or cholesterol absorption inhibitors. − In addition, a macrophage-targeted strategy has been recently emerged as a promising solution for specifically attenuating the progression of atherosclerosis. − …”

Section: Introductionmentioning

confidence: 99%

Ultrasmall Fe(III)-Tannic Acid Nanoparticles To Prevent Progression of Atherosclerotic Plaques

Wang

et al. 2021

ACS Appl. Mater. Interfaces

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Macrophage accumulation is central to the pathogenesis of atherosclerotic plaques. Reducing macrophages in plaques is an appealing approach to attenuate the development of atherosclerosis. Chemodynamic therapy, specifically inhibiting hydrogen peroxide (H2O2)-rich cells in slightly acidic microenvironment, has emerged as a new method in tumor treatment. Herein, we manufactured ultrasmall dopamine-modified hyaluronic acid (HD)-stabilized Fe(III)-tannic acid nanoparticles (HFTNPs). HFTNPs can specifically accumulate in inflammatory macrophages in atherosclerotic plaques, provide brighter magnetic resonance images, promote reactive oxygen species (ROS) generation, and induce the death of inflammatory macrophages without damaging normal cells and tissues. In conclusion, HFTNPs have a tremendous potential as safe and effective diagnostic and therapeutic reagents for atherosclerosis.

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Applications of inorganic nanoparticles in the diagnosis and therapy of atherosclerosis

Abstract: This review focuses on recent advances in inorganic nanoparticles based dual-model imaging and therapeutic approaches for anti-atherosclerosis, including clinical trials.

Cited by 61 publications

References 120 publications

Hyaluronic Acid-Functionalized Mesoporous Silica Nanoparticles Loading Simvastatin for Targeted Therapy of Atherosclerosis

Hyaluronic Acid-Functionalized Mesoporous Silica Nanoparticles Loading Simvastatin for Targeted Therapy of Atherosclerosis

Low‐Intensity Focused Ultrasound‐Responsive Ferrite‐Encapsulated Nanoparticles for Atherosclerotic Plaque Neovascularization Theranostics

Ultrasmall Fe(III)-Tannic Acid Nanoparticles To Prevent Progression of Atherosclerotic Plaques

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