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纳米颗粒介导的肿瘤相关血小板的耗竭破坏了血管屏障并增加了肿瘤中的药物积累

时间:2024-08-17      阅读:227

中文摘要:

有限的肿瘤内灌注和纳米颗粒保留仍然是将纳米颗粒疗法递送至肿瘤的主要瓶颈。在这里,我们展示了递送抗血小板抗体 R300 和化疗剂阿霉素的聚合物-脂质-肽纳米颗粒可以局部消耗肿瘤相关的血小板,从而增强血管通透性并增加纳米颗粒在肿瘤中的积累。R300 在纳米颗粒的脂质-肽壳裂解时通过基质金属蛋白酶 2 在肿瘤中特异性释放,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,增强肿瘤通透性。我们还表明,这种策略导致小鼠的实质性肿瘤消退和转移抑制。

英文摘要:

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.


论文信息:

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

中文题目:纳米颗粒介导的肿瘤相关血小板的局部耗竭破坏了血管屏障并增加了肿瘤中的药物积累

期刊名称:Nature Biomedical Engineering

时间期卷:Nature Biomedical Engineering volume 1, pages667–679 (2017)pages685–700 (2024)

在线时间:2017年7月24日


剂量方案:

纳米颗粒介导的肿瘤相关血小板的耗竭破坏了血管屏障并增加了肿瘤中的药物积累

材料方法:

Antibodies for Mouse Platelet Depletion Antibodies R300 is an antibody targeting mouse plateletlet-clearing and is a mixture of purified rat monoclonal antibodies against mouse GPIbα (CD42b). Emfret货号R300抗体是Antibodies for Mouse Platelet Depletion血小板清除抗体,是靶向小鼠血小板清除的抗体,是混合物,包含抗小鼠 GPIbα (CD42b) 的纯化大鼠单克隆抗体。可以参考这篇文献。

纳米颗粒介导的肿瘤相关血小板的耗竭破坏了血管屏障并增加了肿瘤中的药物积累

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