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    Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours

    Authiors: Suping LiYinlong ZhangJing WangYing ZhaoTianjiao JiXiao ZhaoYanping DingXiaozheng ZhaoRuifang ZhaoFeng LiXiao YangShaoli LiuZhaofei LiuJianhao LaiAndrew K. Whittaker, Gregory J. AndersonJingyan Wei & Guangjun Nie

    Nature Biomedical Engineering 2017, 1 (8), 667-679.

    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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