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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Main Authors: Lihe Sun, Juan Ouyang, Zhuo Zeng, Cheng Zeng, Yunqing Ma, Fang Zeng, Shuizhu Wu
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-04-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21003868
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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
collection DOAJ
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.
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spelling doaj.art-3a1280ad6a4b49459f3444cd6b3e4fab2024-04-17T03:38:59ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-04-01107992Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathwaysLihe Sun0Juan Ouyang1Zhuo Zeng2Cheng Zeng3Yunqing Ma4Fang Zeng5Shuizhu Wu6Biomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, ChinaBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, ChinaBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, ChinaBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, ChinaBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, ChinaCorresponding author.; Biomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, ChinaCorresponding author.; Biomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, ChinaImmune-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.http://www.sciencedirect.com/science/article/pii/S2452199X21003868Actively-targeting nanosystemImmune-mediated inflammatory diseaseTwo-mode imagingNF-κB/NLRP3 pathways
spellingShingle 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
Bioactive Materials
Actively-targeting nanosystem
Immune-mediated inflammatory disease
Two-mode imaging
NF-κB/NLRP3 pathways
title 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_short 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
topic Actively-targeting nanosystem
Immune-mediated inflammatory disease
Two-mode imaging
NF-κB/NLRP3 pathways
url http://www.sciencedirect.com/science/article/pii/S2452199X21003868
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