Imperial College London
Alternate

ProfessorRongjunChen

Faculty of Engineering, Department of Chemical Engineering

Professor of Biomaterials Engineering
 
 
 
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Contact

 

+44 (0)20 7594 2070rongjun.chen Website

 
 
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Location

 

408ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Huang:2022:10.1002/adhm.202201265,
author = {Huang, Y and Jiang, J and Ren, J and Guo, Y and Zhao, Q and Zhou, J and Li, Y and Chen, R},
doi = {10.1002/adhm.202201265},
journal = {Advanced Healthcare Materials},
pages = {1--17},
title = {A fibrinogen-mimicking, activated-platelet-sensitive nanocoacervate enhances thrombus targeting and penetration of tissue plasminogen activator for effective thrombolytic therapy.},
url = {http://dx.doi.org/10.1002/adhm.202201265},
volume = {11},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Development of a fibrinolytic system with long circulation time, high thrombus targeting, efficient thrombus penetration, effective thrombolysis and minimal hemorrhagic risk remains a major challenge. Herein, inspired by fibrinogen binding to activated platelets in thrombosis, we report a fibrinogen-mimicking, activated-platelet-sensitive nanocoacervate to enhance thrombus penetration of tissue plasminogen activator (tPA) for targeted thrombolytic therapy. This biomimetic nanothrombolytic system, denoted as RGD-Chi@tPA, was constructed by "one-pot" coacervation through electrostatic interactions between positively charged arginine-glycine-aspartic acid (RGD)-grafted chitosan (RGD-Chi) and negatively charged tPA. Flow cytometry and confocal laser scanning microscopy measurements showed a targeting of RGD-Chi@tPA to activated platelets. Controlled tPA release triggered by activated platelets at a thrombus site was demonstrated. Its targeted fibrinolytic and thrombolytic activities were measured in vitro models. The pharmacokinetic profiles showed that RGD-Chi@tPA could significantly prolong circulation time compared to free tPA. In a mouse tail thrombus model, RGD-Chi@tPA displayed efficient thrombus targeting and penetration, enabling a complete vascular recanalization as confirmed by the fluorescence imaging, histochemical assay and laser speckle contrast imager. Consequently, RGD-Chi@tPA induced a substantial enhancement in thrombolysis with minimal hemorrhagic risk compared to free tPA. This simple, effective and safe platform holds a great promise for development of thrombolytic nanomedicines. This article is protected by copyright. All rights reserved.
AU  - Huang,Y
AU  - Jiang,J
AU  - Ren,J
AU  - Guo,Y
AU  - Zhao,Q
AU  - Zhou,J
AU  - Li,Y
AU  - Chen,R
DO  - 10.1002/adhm.202201265
EP  - 17
PY  - 2022///
SN  - 2192-2640
SP  - 1
TI  - A fibrinogen-mimicking, activated-platelet-sensitive nanocoacervate enhances thrombus targeting and penetration of tissue plasminogen activator for effective thrombolytic therapy.
T2  - Advanced Healthcare Materials
UR  - http://dx.doi.org/10.1002/adhm.202201265
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35864062
UR  - https://onlinelibrary.wiley.com/doi/10.1002/adhm.202201265
UR  - http://hdl.handle.net/10044/1/98574
VL  - 11
ER  -
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