Wayne Elizabeth C, Chandrasekaran Siddarth, Mitchell Michael J, Chan Maxine F, Lee Rachel E, Schaffer Chris B, King Michael R
Meinig School of Biomedical Engineering, Cornell University, 526 N. Campus Rd, Weill Hall, Ithaca, NY 14853, United States.
Meinig School of Biomedical Engineering, Cornell University, 526 N. Campus Rd, Weill Hall, Ithaca, NY 14853, United States.
J Control Release. 2016 Feb 10;223:215-223. doi: 10.1016/j.jconrel.2015.12.048. Epub 2015 Dec 28.
Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells. We conclude that the use of circulating leukocytes as a carrier for the anti-cancer protein TRAIL could be an effective tool to directly target circulating tumor cells for the prevention of prostate cancer metastasis, and potentially other cancers that spread through the bloodstream.
前列腺癌一旦从局部发展为转移形式,就是一种预后不良且治疗选择有限的疾病。在此,我们展示了一种方法,即使用与E-选择素粘附蛋白和Apo2L/TRAIL(肿瘤坏死因子相关凋亡诱导配体)凋亡配体偶联的纳米级脂质体,这些脂质体附着于白细胞表面,并能迅速从活体小鼠的循环血液中清除存活的癌细胞。首次表明,通过大幅减少循环肿瘤细胞的数量,这种方法可用于预防前列腺癌原位异种移植模型中转移性肿瘤的自发形成和生长。我们得出结论,利用循环白细胞作为抗癌蛋白TRAIL的载体,可能是直接靶向循环肿瘤细胞以预防前列腺癌转移以及潜在预防其他通过血液传播的癌症的有效工具。