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首页> 外文期刊>EBioMedicine >Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery
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Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery

机译：胰腺导管腺癌中的异位性高内皮小静脉：靶向递送的独特位点

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Background Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79. Methods Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC. Findings The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was more robust than non-conjugated NPs. Treatment with MECA79-Taxol-NPs augmented the delivery of Paclitaxel (Taxol) to the tumor site and significantly reduced the tumor size. This effect was associated with a higher apoptosis rate of PDAC cells and reduced vascularization within the tumor. Interpretation Targeting the HEVs of PDAC using MECA79-NPs could lay the ground for the localized delivery of a wide variety of drugs including chemotherapeutic agents. Fund National Institutes of Health (NIH) grants: T32-EB016652 (B·B.), NIH Cancer Core Grant CA034196 (L.D.S.), National Institute of Allergy and Infectious Diseases grants R01-AI126596 and R01-HL141815 (R.A.).
机译：背景技术纳米医学通过增强治疗药物向肿瘤部位的递送，为治疗难治性恶性肿瘤提供了极好的机会。高内皮小静脉（HEVs）主要在炎症反应期间在淋巴结中发现或在周围组织中从头形成。它们表达被单克隆抗体MECA79识别的外围结节蛋白（PNAd）。方法在这里，我们证明了HEV在人胰管腺癌（PDAC）中从头形成。我们设计了可识别PDAC中这些异位HEV的MECA79涂层纳米颗粒（MECA79-NP）。研究结果在静脉内递送至人源化小鼠模型中植入的人PDAC后，MECA79-NP的转运比非结合的NP更有力。用MECA79-紫杉醇-NPs治疗增加了紫杉醇（紫杉醇）到肿瘤部位的递送并显着减小了肿瘤的大小。该作用与PDAC细胞的较高凋亡率和肿瘤内血管形成减少有关。解释使用MECA79-NPs靶向PDAC的HEV可能为局部递送包括化疗药物在内的多种药物奠定基础。美国国立卫生研究院（NIH）基金：T32-EB016652（B.B.），美国国立卫生研究院癌症核心补助金CA034196（L.D.S.），美国过敏和传染病研究所（NIH）资助R01-AI126596和R01-HL141815（R.A.）。

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