Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways

Immune-mediated inflammatory diseases (IMIDs) represent a diverse group of diseases and challenges remain for the current medications. Herein, we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways. A ROS-activat...

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Autores principales: Lihe Sun, Juan Ouyang, Zhuo Zeng, Cheng Zeng, Yunqing Ma, Fang Zeng, Shuizhu Wu
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Publicado: KeAi Communications Co., Ltd. 2022
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spelling oai:doaj.org-article:3a1280ad6a4b49459f3444cd6b3e4fab2021-11-26T04:36:40ZTargeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways2452-199X10.1016/j.bioactmat.2021.08.010https://doaj.org/article/3a1280ad6a4b49459f3444cd6b3e4fab2022-04-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21003868https://doaj.org/toc/2452-199XImmune-mediated inflammatory diseases (IMIDs) represent a diverse group of diseases and challenges remain for the current medications. Herein, we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways. A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate (EGCG) through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety. BH-EGCG molecules readily form stable nanoparticles in aqueous medium, which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites. Additionally, an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy. Benefiting from the inflammation-homing effect of the macrophage membrane, the nanosystem delivers payloads (diagnostic probe and therapeutic drugs) to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS, thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models, including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation. This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.Lihe SunJuan OuyangZhuo ZengCheng ZengYunqing MaFang ZengShuizhu WuKeAi Communications Co., Ltd.articleActively-targeting nanosystemImmune-mediated inflammatory diseaseTwo-mode imagingNF-κB/NLRP3 pathwaysMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 10, Iss , Pp 79-92 (2022)
institution DOAJ
collection DOAJ
language EN
topic Actively-targeting nanosystem
Immune-mediated inflammatory disease
Two-mode imaging
NF-κB/NLRP3 pathways
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
spellingShingle Actively-targeting nanosystem
Immune-mediated inflammatory disease
Two-mode imaging
NF-κB/NLRP3 pathways
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
Lihe Sun
Juan Ouyang
Zhuo Zeng
Cheng Zeng
Yunqing Ma
Fang Zeng
Shuizhu Wu
Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways
description Immune-mediated inflammatory diseases (IMIDs) represent a diverse group of diseases and challenges remain for the current medications. Herein, we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways. A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate (EGCG) through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety. BH-EGCG molecules readily form stable nanoparticles in aqueous medium, which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites. Additionally, an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy. Benefiting from the inflammation-homing effect of the macrophage membrane, the nanosystem delivers payloads (diagnostic probe and therapeutic drugs) to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS, thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models, including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation. This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.
format article
author Lihe Sun
Juan Ouyang
Zhuo Zeng
Cheng Zeng
Yunqing Ma
Fang Zeng
Shuizhu Wu
author_facet Lihe Sun
Juan Ouyang
Zhuo Zeng
Cheng Zeng
Yunqing Ma
Fang Zeng
Shuizhu Wu
author_sort Lihe Sun
title Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways
title_short Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways
title_full Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways
title_fullStr Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways
title_full_unstemmed Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways
title_sort targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting nf-κb/nlrp3 pathways
publisher KeAi Communications Co., Ltd.
publishDate 2022
url https://doaj.org/article/3a1280ad6a4b49459f3444cd6b3e4fab
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