TY - JOUR
T1 - Engineered Nanoplatelets for Targeted Delivery of Plasminogen Activators to Reverse Thrombus in Multiple Mouse Thrombosis Models
AU - Xu, Junchao
AU - Zhang, Yinlong
AU - Xu, Jiaqi
AU - Liu, Guangna
AU - Di, Chunzhi
AU - Zhao, Xiao
AU - Li, Xiang
AU - Li, Yao
AU - Pang, Ningbo
AU - Yang, Chengzhi
AU - Li, Yanyi
AU - Li, Bozhao
AU - Lu, Zefang
AU - Wang, Meifang
AU - Dai, Kesheng
AU - Yan, Rong
AU - Li, Suping
AU - Nie, Guangjun
N1 - Funding Information:
This work was supported by the National Key R&D Program of China (Grant Nos. 2018YFE0205300 and 2018YFA0208900), the National Natural Science Foundation of China (Grant Nos. 31900992, 31730032, 31661130152, and 31471035), a Key Research Project of Frontier Science of the Chinese Academy of Sciences (Grant No. QYZDJ-SSW-SLH022), Beijing Natural Science Foundation (Grant No. 7172164), Beijing Municipal Natural Science Foundation (7182126), the National Postdoctoral Program for Innovative Talents (BX20180083), Youth Innovation Promotion Association CAS (Grant No. 2017056), and K. C. Wong Education Foundation (GJTD-2018-03).
Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Rapid cut-off of blood supply in diseases involving thrombosis is a major cause of morbidity and mortality worldwide. However, the current thrombolysis strategies offer limited results due to the therapeutics' short half-lives, low targeting ability, and unexpected bleeding complications. Inspired by the innate roles of platelets in hemostasis and pathological thrombus, platelet membrane-camouflaged polymeric nanoparticles (nanoplatelets) are developed for targeting delivery of the thrombolytic drug, recombinant tissue plasminogen activator (rt-PA), to local thrombus sites. The tailor-designed nanoplatelets efficiently accumulate at the thrombi in pulmonary embolism and mesenteric arterial thrombosis model mice, eliciting a significantly enhanced thrombolysis activity compared to free rt-PA. In addition, the nanoplatelets exhibit improved therapeutic efficacy over free rt-PA in an ischemic stroke model. Analysis of in vivo coagulation indicators suggests the nanoplatelets might possess a low risk of bleeding complications. The hybrid biomimetic nanoplatelets described offer a promising solution to improve the efficacy and reduce the bleeding risk of thrombolytic therapy in a broad spectrum of thrombosis diseases.
AB - Rapid cut-off of blood supply in diseases involving thrombosis is a major cause of morbidity and mortality worldwide. However, the current thrombolysis strategies offer limited results due to the therapeutics' short half-lives, low targeting ability, and unexpected bleeding complications. Inspired by the innate roles of platelets in hemostasis and pathological thrombus, platelet membrane-camouflaged polymeric nanoparticles (nanoplatelets) are developed for targeting delivery of the thrombolytic drug, recombinant tissue plasminogen activator (rt-PA), to local thrombus sites. The tailor-designed nanoplatelets efficiently accumulate at the thrombi in pulmonary embolism and mesenteric arterial thrombosis model mice, eliciting a significantly enhanced thrombolysis activity compared to free rt-PA. In addition, the nanoplatelets exhibit improved therapeutic efficacy over free rt-PA in an ischemic stroke model. Analysis of in vivo coagulation indicators suggests the nanoplatelets might possess a low risk of bleeding complications. The hybrid biomimetic nanoplatelets described offer a promising solution to improve the efficacy and reduce the bleeding risk of thrombolytic therapy in a broad spectrum of thrombosis diseases.
KW - nanoplatelets
KW - plasminogen activators
KW - targeted drug delivery
KW - thrombus
KW - Recombinant Proteins/biosynthesis
KW - Thrombosis/drug therapy
KW - Polymers/chemistry
KW - Drug Carriers/chemistry
KW - Tissue Plasminogen Activator/chemistry
KW - Animals
KW - Fibrinolytic Agents/chemistry
KW - Nanoparticles/chemistry
KW - Mice
KW - Disease Models, Animal
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U2 - 10.1002/adma.201905145
DO - 10.1002/adma.201905145
M3 - Article
C2 - 31788896
AN - SCOPUS:85076162793
SN - 0935-9648
VL - 32
SP - e1905145
JO - Advanced Materials
JF - Advanced Materials
IS - 4
M1 - 1905145
ER -