Platelet mediated TRAIL delivery for efficiently targeting circulating tumor cells.
Platelet mediated TRAIL delivery for efficiently targeting circulating tumor cells.
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DOI：
10.1039/d0na00271b
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发表时间：
2020-09-16
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
一些研究已经证明了血小板在促进癌症转移中的作用。血小板结合并保护循环肿瘤细胞（CTC）免受血液动力学力和免疫细胞的影响，并且还促进肿瘤细胞在脉管系统中的停滞和外渗。因此，血小板代表将抗癌治疗剂递送至CTC的有前景的媒介物。在这项研究中，我们开发了一种新的血小板介导的肿瘤坏死因子相关的凋亡诱导配体（TRAIL）传递系统，以靶向CTC和阻碍转移通过“原位”血小板修饰。这种血小板介导的TRAIL递送显著降低了在生理剪切条件下流动血液中循环的结直肠癌和乳腺癌细胞的活力。TRAIL包被的血小板显著地杀死来自多种原发性转移性癌症样品的流动血液中超过60%的CTC。由于血小板与循环中的癌细胞相互作用，血小板被认为是转移调节的重要参与者;目前的研究支持使用基于血小板的TRAIL递送作为有希望的CTC靶向癌症治疗的想法。脂质体制剂通过血管性血友病因子（vWF）相互作用向血小板递送TNF相关的凋亡诱导配体（TRAIL）。TRAIL包被的血小板杀死血液中的循环肿瘤细胞（CTC），以减少癌症转移。
Several studies have demonstrated the role of platelets in promoting cancer metastasis. Platelets bind to and protect circulating tumor cells (CTCs) from hemodynamic forces and immune cells, and also promote tumor cell arrest in the vasculature and extravasation. Thus, platelets represent a promising vehicle to deliver anticancer therapeutic agents to CTCs. In this study, we developed a novel platelet-mediated TNF-related apoptosis inducing ligand (TRAIL) delivery system to target CTCs and hinder metastasis via “in situ” platelet modification. This platelet-mediated TRAIL delivery significantly reduced the viability of colorectal and breast cancer cells circulating in flowing blood under physiological shear conditions. TRAIL-coated platelets significantly killed over 60% of CTCs in flowing blood from a variety of primary metastatic cancer samples. Platelets have been considered an important player in the regulation of metastasis due to their interaction with cancer cells in the circulation; the current study supports the idea of using platelet-based TRAIL delivery as a promising CTC-targeted cancer therapy. Liposomal formulation to deliver TNF-related apoptosis-inducing ligand (TRAIL) to platelets via von Willebrand Factor (vWF) interaction. TRAIL-coated platelets killed circulating tumor cells (CTCs) in the bloodstream to reduce cancer metastasis.
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影响因子：
3.8
作者：
Khan UT;Walker AJ;Baig S;Card TR;Kirwan CC;Grainge MJ
通讯作者：
Grainge MJ
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
6.1
作者：
Chandrasekaran, Siddarth;McGuire, Matthew J.;King, Michael R.
通讯作者：
King, Michael R.
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
3.7
作者：
Barnes, J. Matthew;Nauseef, Jones T.;Henry, Michael D.
通讯作者：
Henry, Michael D.