納米顆粒介導(dǎo)的腫瘤相關(guān)血小板的耗竭破壞了血管屏障并增加了腫瘤中的藥物積累

中文摘要：

有限的腫瘤內(nèi)灌注和納米顆粒保留仍然是將納米顆粒療法遞送至腫瘤的主要瓶頸。在這里，我們展示了遞送抗血小板抗體 R300 和化療劑阿霉素的聚合物-脂質(zhì)-肽納米顆粒可以局部消耗腫瘤相關(guān)的血小板，從而增強血管通透性并增加納米顆粒在腫瘤中的積累。R300 在納米顆粒的脂質(zhì)-肽殼裂解時通過基質(zhì)金屬蛋白酶 2 在腫瘤中特異性釋放，金屬蛋白酶 2 通常在腫瘤血管內(nèi)皮和基質(zhì)中過表達，從而促進血管破裂，增強腫瘤通透性。我們還表明，這種策略導(dǎo)致小鼠的實質(zhì)性腫瘤消退和轉(zhuǎn)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.

論文信息：

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

中文題目：納米顆粒介導(dǎo)的腫瘤相關(guān)血小板的局部耗竭破壞了血管屏障并增加了腫瘤中的藥物積累

期刊名稱：Nature Biomedical Engineering

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

在線時間：2017年7月24日

劑量方案：

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貨號R300抗體是Antibodies for Mouse Platelet Depletion血小板清除抗體,是靶向小鼠血小板清除的抗體,是混合物,包含抗小鼠 GPIbα (CD42b) 的純化大鼠單克隆抗體。可以參考這篇文獻。