Complement‐Opsonized NIR‐IIb Emissive Immunotracers for Dynamically Monitoring Neutrophils in Inflammation‐Related Diseases

Real‐time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation‐related diseases, which requires a reliable tracer for in vivo tracking of neutrophils. However, immunotracers for neutrophils are extremely limited because of the difficulty in labeli...

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Published inAdvanced materials (Weinheim) Vol. 34; no. 34; pp. e2203477 - n/a
Main Authors Zhang, Meng, Wang, Zijun, Shao, Yunlong, Zhao, Yaoyao, Liu, Zhihong
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 01.08.2022
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Abstract Real‐time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation‐related diseases, which requires a reliable tracer for in vivo tracking of neutrophils. However, immunotracers for neutrophils are extremely limited because of the difficulty in labeling the cells. Inspired by the natural biological function of the complement system, a strategy of enhancing the complement C3 opsonization of lanthanide‐doped nanoparticles (LnNPs) by modulating their surface chemistry, thus developing a near infrared‐IIb emissive nanotracer for neutrophils, is reported herein. Four kinds of surface‐modified LnNPs are fabricated, among which phospholipids DOPG‐modified LnNPs (LnNPs@PG) with weak antifouling ability and hydroxyl groups adsorb more complement C3 proteins and form covalent linkages with C3b active fragments under inflammation conditions, inducing enhanced complement C3 opsonization. Therefore, LnNPs@PG with enhanced complement C3 opsonization are capable of efficiently labeling inflammation‐stimulated neutrophils in vivo through complement‐receptors‐mediated phagocytosis and achieve dynamic monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion. Complement C3 opsonized near‐infrared‐IIb emissive immunotracers are captured by inflammation‐stimulated neutrophils in circulatory blood through complement‐receptors‐mediated phagocytosis, enabling dynamically monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion. The strategy of modulating surface chemistry of nanosized imaging agents to enhance complement C3 opsonization provides a new insight to develop immunotracers for in vivo labeling and tracking neutrophils.
AbstractList Real‐time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation‐related diseases, which requires a reliable tracer for in vivo tracking of neutrophils. However, immunotracers for neutrophils are extremely limited because of the difficulty in labeling the cells. Inspired by the natural biological function of the complement system, a strategy of enhancing the complement C3 opsonization of lanthanide‐doped nanoparticles (LnNPs) by modulating their surface chemistry, thus developing a near infrared‐IIb emissive nanotracer for neutrophils, is reported herein. Four kinds of surface‐modified LnNPs are fabricated, among which phospholipids DOPG‐modified LnNPs (LnNPs@PG) with weak antifouling ability and hydroxyl groups adsorb more complement C3 proteins and form covalent linkages with C3b active fragments under inflammation conditions, inducing enhanced complement C3 opsonization. Therefore, LnNPs@PG with enhanced complement C3 opsonization are capable of efficiently labeling inflammation‐stimulated neutrophils in vivo through complement‐receptors‐mediated phagocytosis and achieve dynamic monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion.
Real‐time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation‐related diseases, which requires a reliable tracer for in vivo tracking of neutrophils. However, immunotracers for neutrophils are extremely limited because of the difficulty in labeling the cells. Inspired by the natural biological function of the complement system, a strategy of enhancing the complement C3 opsonization of lanthanide‐doped nanoparticles (LnNPs) by modulating their surface chemistry, thus developing a near infrared‐IIb emissive nanotracer for neutrophils, is reported herein. Four kinds of surface‐modified LnNPs are fabricated, among which phospholipids DOPG‐modified LnNPs (LnNPs@PG) with weak antifouling ability and hydroxyl groups adsorb more complement C3 proteins and form covalent linkages with C3b active fragments under inflammation conditions, inducing enhanced complement C3 opsonization. Therefore, LnNPs@PG with enhanced complement C3 opsonization are capable of efficiently labeling inflammation‐stimulated neutrophils in vivo through complement‐receptors‐mediated phagocytosis and achieve dynamic monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion. Complement C3 opsonized near‐infrared‐IIb emissive immunotracers are captured by inflammation‐stimulated neutrophils in circulatory blood through complement‐receptors‐mediated phagocytosis, enabling dynamically monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion. The strategy of modulating surface chemistry of nanosized imaging agents to enhance complement C3 opsonization provides a new insight to develop immunotracers for in vivo labeling and tracking neutrophils.
Abstract Real‐time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation‐related diseases, which requires a reliable tracer for in vivo tracking of neutrophils. However, immunotracers for neutrophils are extremely limited because of the difficulty in labeling the cells. Inspired by the natural biological function of the complement system, a strategy of enhancing the complement C3 opsonization of lanthanide‐doped nanoparticles (LnNPs) by modulating their surface chemistry, thus developing a near infrared‐IIb emissive nanotracer for neutrophils, is reported herein. Four kinds of surface‐modified LnNPs are fabricated, among which phospholipids DOPG‐modified LnNPs (LnNPs@PG) with weak antifouling ability and hydroxyl groups adsorb more complement C3 proteins and form covalent linkages with C3b active fragments under inflammation conditions, inducing enhanced complement C3 opsonization. Therefore, LnNPs@PG with enhanced complement C3 opsonization are capable of efficiently labeling inflammation‐stimulated neutrophils in vivo through complement‐receptors‐mediated phagocytosis and achieve dynamic monitoring neutrophils during cutaneous wound healing and cerebral ischemia/reperfusion.
Author Zhao, Yaoyao
Liu, Zhihong
Zhang, Meng
Wang, Zijun
Shao, Yunlong
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Snippet Real‐time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation‐related diseases, which requires a reliable...
Abstract Real‐time monitoring of neutrophil dynamics is crucial for timely diagnosis and effective treatment of inflammation‐related diseases, which requires a...
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SubjectTerms Complement
complement C3 opsonization
Hydroxyl groups
in vivo tracking
Inflammation
Labeling
lanthanide‐doped nanoparticles
Materials science
Monitoring
Nanoparticles
Neutrophils
NIR‐II fluorescence imaging
Phospholipids
Wound healing
Title Complement‐Opsonized NIR‐IIb Emissive Immunotracers for Dynamically Monitoring Neutrophils in Inflammation‐Related Diseases
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fadma.202203477
https://www.proquest.com/docview/2705966318/abstract/
https://search.proquest.com/docview/2685445675
Volume 34
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