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1.
J Med Chem ; 67(14): 12428-12438, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38996002

RESUMEN

Targeting Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages using RNAi nanotechnology represents an innovative and promising strategy in the diagnosis and treatment of atherosclerosis. Nevertheless, it remains elusive because of the current challenges associated with the systemic delivery of siRNA nanoparticle (NP) to atheromatous plaques and the complexity of atherosclerotic plaques. Here, we demonstrate the potential of a thienothiadiazole-based near-infrared-II (NIR-II) organic aggregation-induced emission (AIE) platform encapsulated with the Camk2g siRNA to effectively target CaMKIIγ in macrophages for dynamic imaging and image-guided gene therapy of atherosclerosis. The nanoparticles effectively decreased CaMKIIγ expression and increased the expression of the efferocytosis receptor MerTK in plaque macrophages, leading to a reduction in the necrotic core area of the lesion in an aortic plaque model. Our theranostic approach highlights the substantial promise of near-infrared II (NIR-II) AIEgens for imaging and image-guided therapy of atherosclerosis.


Asunto(s)
Aterosclerosis , Imagen Óptica , ARN Interferente Pequeño , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/terapia , ARN Interferente Pequeño/química , ARN Interferente Pequeño/uso terapéutico , Animales , Ratones , Nanopartículas/química , Humanos , Placa Aterosclerótica/diagnóstico por imagen , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Tiadiazoles/química , Tiadiazoles/farmacología , Rayos Infrarrojos
2.
Acta Pharm Sin B ; 13(11): 4578-4590, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37969732

RESUMEN

Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.

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