Imperial College London
Alternate

ProfessorSimonThom

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 7594 1100s.thom

 
 
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Assistant

 

Mrs Yvonne Green +44 (0)20 7594 1100

 
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Location

 

330ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Huang:2019:10.1016/j.jconrel.2019.02.033,
author = {Huang, Y and Yu, L and Ren, J and Gu, B and Longstaff, C and Hughes, AD and Thom, SA and Xu, XY and Chen, R},
doi = {10.1016/j.jconrel.2019.02.033},
journal = {Journal of Controlled Release},
pages = {1--12},
title = {An activated-platelet-sensitive nanocarrier enables targeted delivery of tissue plasminogen activator for effective thrombolytic therapy},
url = {http://dx.doi.org/10.1016/j.jconrel.2019.02.033},
volume = {300},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - It remains a major challenge to develop a selective and effective fibrinolytic system for thrombolysis with minimal undesirable side effects. Herein, we report a multifunctional liposomal system (164.6±5.3nm in diameter) which can address this challenge through targeted delivery and controlled release of tissue plasminogen activator (tPA) at the thrombus site. The tPA-loaded liposomes were PEGylated to improve their stability, and surface coated with a conformationally-constrained, cyclic arginine-glycine-aspartic acid (cRGD) to enable highly selective binding to activated platelets. The in vitro drug release profiles at 37°C showed that over 90% of tPA was released through liposomal membrane destabilization involving membrane fusion upon incubation with activated platelets within 1h, whereas passive release of the encapsulated tPA in pH 7.4 PBS buffer was 10% after 6h. The release of tPA could be readily manipulated by changing the concentration of activated platelets. The presence of activated platelets enabled the tPA-loaded, cRGD-coated, PEGylated liposomes to induce efficient fibrin clot lysis in a fibrin-agar plate model and the encapsulated tPA retained 97.4±1.7% of fibrinolytic activity as compared with that of native tPA. Furthermore, almost complete blood clot lysis was achieved in 75min, showing considerably higher and quicker thrombolytic activity compared to the tPA-loaded liposomes without cRGD labelling. These results suggest that the nano-sized, activated-platelet-sensitive, multifunctional liposomes could facilitate selective delivery and effective release of tPA at the site of thrombus, thus achieving efficient clot dissolution whilst minimising undesirable side effects.
AU  - Huang,Y
AU  - Yu,L
AU  - Ren,J
AU  - Gu,B
AU  - Longstaff,C
AU  - Hughes,AD
AU  - Thom,SA
AU  - Xu,XY
AU  - Chen,R
DO  - 10.1016/j.jconrel.2019.02.033
EP  - 12
PY  - 2019///
SN  - 0168-3659
SP  - 1
TI  - An activated-platelet-sensitive nanocarrier enables targeted delivery of tissue plasminogen activator for effective thrombolytic therapy
T2  - Journal of Controlled Release
UR  - http://dx.doi.org/10.1016/j.jconrel.2019.02.033
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30807804
UR  - https://www.sciencedirect.com/science/article/pii/S0168365919301166
UR  - http://hdl.handle.net/10044/1/68221
VL  - 300
ER  -
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