Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours
Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours
复制标题
纳米颗粒介导的肿瘤相关血小板的局部消耗会破坏血管屏障并增加肿瘤中的药物积累
DOI：
10.1038/s41551-017-0115-8
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发表时间：
2017-08-01
影响因子：
28.1
通讯作者：
Nie, Guangjun
中科院分区：
文献类型：
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作者：
Li, Suping;Zhang, Yinlong;Nie, Guangjun
有限的肿瘤内灌注和纳米颗粒保留仍然是将纳米颗粒治疗剂递送到肿瘤中的主要瓶颈。在这里，我们表明，聚合物-脂质-肽纳米颗粒提供的抗血小板抗体R300和化疗剂阿霉素可以局部耗尽肿瘤相关的血小板，从而提高血管通透性和增加的纳米颗粒在肿瘤中的积累。R300在纳米颗粒的脂质-肽壳被基质金属蛋白酶2裂解时特异性地释放到肿瘤中，基质金属蛋白酶2通常在肿瘤血管内皮和基质中过表达，从而促进血管破裂，增强肿瘤渗透性。我们还表明，这种策略导致小鼠的肿瘤消退和转移抑制。
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.