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采用岩藻糖结合纳米颗粒方法靶向胰腺癌癌细胞的抗癌药物递送。

Targeting anticancer drug delivery to pancreatic cancer cells using a fucose-bound nanoparticle approach.

机构信息

Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

PLoS One. 2012;7(7):e39545. doi: 10.1371/journal.pone.0039545. Epub 2012 Jul 11.

Abstract

Owing to its aggressiveness and the lack of effective therapies, pancreatic ductal adenocarcinoma has a dismal prognosis. New strategies to improve treatment and survival are therefore urgently required. Numerous fucosylated antigens in sera serve as tumor markers for cancer detection and evaluation of treatment efficacy. Increased expression of fucosyltransferases has also been reported for pancreatic cancer. These enzymes accelerate malignant transformation through fucosylation of sialylated precursors, suggesting a crucial requirement for fucose by pancreatic cancer cells. With this in mind, we developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specifically to cancer cells. L-fucose-bound liposomes containing Cy5.5 or Cisplatin were effectively delivered into CA19-9 expressing pancreatic cancer cells. Excess L-fucose decreased the efficiency of Cy5.5 introduction by L-fucose-bound liposomes, suggesting L-fucose-receptor-mediated delivery. Intravenously injected L-fucose-bound liposomes carrying Cisplatin were successfully delivered to pancreatic cancer cells, mediating efficient tumor growth inhibition as well as prolonging survival in mouse xenograft models. This modality represents a new strategy for pancreatic cancer cell-targeting therapy.

摘要

由于其侵袭性和缺乏有效的治疗方法,胰腺导管腺癌的预后很差。因此,迫切需要新的策略来改善治疗效果和生存率。血清中许多岩藻糖基化抗原可作为癌症检测和治疗效果评估的肿瘤标志物。也有报道称胰腺癌中岩藻糖基转移酶的表达增加。这些酶通过唾液酸化前体的岩藻糖化加速恶性转化,表明胰腺癌细胞对岩藻糖有迫切的需求。考虑到这一点,我们开发了岩藻糖结合的纳米颗粒作为将抗癌药物专门递送到癌细胞的载体。含有 Cy5.5 或顺铂的 L-岩藻糖结合脂质体有效地递送到表达 CA19-9 的胰腺癌细胞中。过量的 L-岩藻糖降低了 L-岩藻糖结合脂质体引入 Cy5.5 的效率,表明是通过 L-岩藻糖受体介导的递送。携带顺铂的静脉注射 L-岩藻糖结合脂质体成功递送到胰腺癌细胞中,介导有效的肿瘤生长抑制,并延长小鼠异种移植模型中的存活时间。这种方式代表了一种针对胰腺癌细胞的靶向治疗的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f61/3394772/bfc16b692ec7/pone.0039545.g001.jpg

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