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Published on: September 25, 2016
Dual RONS-responsive chemiluminescence-guided multimodal thrombolysis based on an aggregation-induced emission
Ziwei Wang1,2, Liping Zhang1, Zihan Wu2
1Department of Neurology, Inst Translat Med, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital Shenzhen 518035 China zhanglp914@nenu.edu.cn rlj2020@email.szu.edu.cn.
Abstract:
Carotid artery thrombosis carries a high risk of disability and mortality. Organic small molecules can be used to create personalized thrombosis theranostics in precision medicine. However, due to poor water solubility, instability, and competition in energy transfer mechanisms involved in imaging and treatment, the development of small-molecule probes with efficient therapeutic performance remains challenging. Herein, we report the first bimetallic, deep-penetrating aggregation-induced emission (AIE) cobalt-porphyrin-based nanoparticles (Co2Ir NPs) that enable the simultaneous "precise targeting, accurate treatment, and effective repair" of thrombosis. Co2Ir NPs undergo dual response to reactive oxygen and nitrogen species (RONS), releasing Co2Ir, which reacts with endogenous ONOO- for chemiluminescence imaging, thereby allowing precise location of a thrombus. Co2Ir generates 1O2 and heat via photodynamic and photothermal therapy (PDT/PTT) under laser irradiation to dissolve thrombus surfaces, while sonodynamic therapy (SDT) drives the NPs into the thrombi to 8 mm penetration depth, with 82% thrombolysis efficiency without secondary embolism. Concurrently, Co2Ir NPs promote vascular reconstruction by upregulating HO-1 expression to exert antioxidant effects, and by downregulating pro-inflammatory factors like TNF-α and IL-6; this dual effect restores the thrombus site to normal. With its exceptional thrombolytic penetration and potent anti-inflammatory effects, this stimulus-responsive chemiluminescent probe holds great promise for the precise visualization and targeted treatment of thrombi.
Insights
New bimetallic nanoparticles offer precise thrombosis treatment. These cobalt-porphyrin-based nanoparticles (Co2Ir NPs) enable targeted imaging, effective thrombolysis, and vascular repair for improved patient outcomes.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Precision Medicine
Background:
- Carotid artery thrombosis poses significant risks of disability and mortality.
- Developing effective theranostics for thrombosis is challenging due to issues with small molecules like poor solubility and instability.
- Existing treatments often lack precision and can lead to complications.
Purpose of the Study:
- To develop novel bimetallic nanoparticles for simultaneous thrombosis imaging, treatment, and repair.
- To overcome the limitations of current small-molecule probes in precision medicine for thrombosis.
- To create a deep-penetrating, stimulus-responsive theranostic agent for carotid artery thrombosis.
Main Methods:
- Synthesized bimetallic, aggregation-induced emission (AIE) cobalt-porphyrin-based nanoparticles (Co2Ir NPs).
- Utilized dual response to reactive oxygen and nitrogen species (RONS) for chemiluminescence imaging and thrombus localization.
- Employed photodynamic/photothermal therapy (PDT/PTT) and sonodynamic therapy (SDT) for thrombolysis with deep penetration.
- Assessed vascular reconstruction by analyzing HO-1 expression and pro-inflammatory factors (TNF-α, IL-6).
Main Results:
- Co2Ir NPs precisely located thrombi via RONS-triggered chemiluminescence.
- Achieved 82% thrombolysis efficiency with deep penetration (8 mm) via PDT/PTT/SDT, avoiding secondary embolism.
- Promoted vascular reconstruction by upregulating HO-1 and downregulating TNF-α and IL-6, restoring normal tissue.
- Demonstrated potent anti-inflammatory effects and exceptional thrombolytic penetration.
Conclusions:
- The developed Co2Ir NPs represent a promising theranostic platform for precise thrombosis visualization and targeted treatment.
- These nanoparticles offer a multi-modal approach combining imaging, deep-penetrating thrombolysis, and anti-inflammatory effects.
- This stimulus-responsive chemiluminescent probe holds significant potential for advancing precision medicine in managing carotid artery thrombosis.
