TY - JOUR
T1 - Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours
AU - Li, Suping
AU - Zhang, Yinlong
AU - Wang, Jing
AU - Zhao, Ying
AU - Ji, Tianjiao
AU - Zhao, Xiao
AU - Ding, Yanping
AU - Zhao, Xiaozheng
AU - Zhao, Ruifang
AU - Li, Feng
AU - Yang, Xiao
AU - Liu, Shaoli
AU - Liu, Zhaofei
AU - Lai, Jianhao
AU - Whittaker, Andrew K.
AU - Anderson, Gregory J.
AU - Wei, Jingyan
AU - Nie, Guangjun
N1 - Funding Information:
The authors thank the cyclotron teams from the Department of Nuclear Medicine, Peking University Cancer Hospital and Institute for the 64Cu production. This work was supported by grants from the National Basic Research Plan of China (2016YFA0201600 and 2013CB932701), National Distinguished Young Scientist Program (31325010), Innovation Group of the National Natural Science Foundation of China (11621505), National Natural Science Foundation of China (31200752, 31661130152, 31470969, 21373067 and 51673051), Frontier Research Program of the Chinese Academy of Sciences (QYZDJ-SSW-SLH022), Beijing Municipal Science and Technology Commission (Z161100000116035), Beijing Nova Program (Z171100001117010), Beijing Natural Science Foundation (7172164) and Youth Innovation Promotion Association of the Chinese Academy of Sciences (2017056).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Limited intratumoural perfusion and nanoparticle retention remain major bottlenecks for the delivery of nanoparticle therapeutics into tumours. Here, we show that polymer-lipid-peptide nanoparticles delivering the antiplatelet antibody R300 and the chemotherapeutic agent doxorubicin can locally deplete tumour-associated platelets, thereby enhancing vascular permeability and augmenting the accumulation of the nanoparticles in tumours. R300 is specifically released in the tumour on cleavage of the lipid-peptide shell of the nanoparticles by matrix metalloprotease 2, which is commonly overexpressed in tumour vascular endothelia and stroma, thus facilitating vascular breaches that enhance tumour permeability. We also show that this strategy leads to substantial tumour regression and metastasis inhibition in mice.
AB - Limited intratumoural perfusion and nanoparticle retention remain major bottlenecks for the delivery of nanoparticle therapeutics into tumours. Here, we show that polymer-lipid-peptide nanoparticles delivering the antiplatelet antibody R300 and the chemotherapeutic agent doxorubicin can locally deplete tumour-associated platelets, thereby enhancing vascular permeability and augmenting the accumulation of the nanoparticles in tumours. R300 is specifically released in the tumour on cleavage of the lipid-peptide shell of the nanoparticles by matrix metalloprotease 2, which is commonly overexpressed in tumour vascular endothelia and stroma, thus facilitating vascular breaches that enhance tumour permeability. We also show that this strategy leads to substantial tumour regression and metastasis inhibition in mice.
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U2 - 10.1038/s41551-017-0115-8
DO - 10.1038/s41551-017-0115-8
M3 - Article
C2 - 31015598
AN - SCOPUS:85031933798
VL - 1
SP - 667
EP - 679
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
SN - 2157-846X
IS - 8
ER -