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CD133 和 CD44 抗体促进纳米颗粒递送至两种胃癌干细胞群体。

The promotion of nanoparticle delivery to two populations of gastric cancer stem cells by CD133 and CD44 antibodies.

机构信息

Department of Pharmacy, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenhe District, Shenyang 110016, PR China.

Department of General Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenhe District, Shenyang 110016, PR China.

出版信息

Biomed Pharmacother. 2019 Jul;115:108857. doi: 10.1016/j.biopha.2019.108857. Epub 2019 Apr 29.

Abstract

Gastric cancer which starts from the stomach is a fatal cancer with poor prognosis around the world. The recurrence and metastasis of gastric cancer may be attributed to gastric cancer stem cells. It is recognized that cancer usually possesses multiple populations of distinct cancer stem cells with different phenotypes, thus it will be imperative to target more subsets of cancer stem cells instead of targeting only one population of cancer stem cells. It is generally accepted that both CD44 and CD133 are gastric cancer stem cells markers, we hereby developed CD44/CD133-ATRA-PLPN (CD44 and CD133 antibody-conjugated all-trans retinoic acid-loaded poly(lactide-co-glycolide)-lecithin-PEG nanoparticles) to target both CD133 and CD44 gastric cancer stem cells. In this study, the therapeutic effect of CD44/CD133-ATRA-PLPN against gastric cancer stem cells was investigated. The results presented here confirmed that CD44/CD133-ATRA-PLPN was efficiently and specifically delivered to CD44 or CD133 gastric cancer stem cells, resulting in enhanced growth inhibitory effect towards gastric cancer stem cells compared with single targeted and non-targeted nanoparticles. As far as we know, we firstly reported the promotion of nanoparticle delivery to two populations of gastric cancer stem cells by antibodies. Since cancer usually contains distinct populations of cancer stem cells with multiple phenotypes, our dual targeting nanoparticles constitute an effective drug delivery platform for targeting multiple populations of cancer stem cells within the cancer.

摘要

胃癌起源于胃部,是一种在全球范围内预后较差的致命癌症。胃癌的复发和转移可能归因于胃癌干细胞。人们认识到,癌症通常具有多个具有不同表型的不同癌症干细胞群体,因此靶向更多的癌症干细胞亚群而不是仅靶向一个癌症干细胞群体将是至关重要的。通常认为 CD44 和 CD133 都是胃癌干细胞标志物,我们在此开发了 CD44/CD133-ATRA-PLPN(CD44 和 CD133 抗体偶联全反式视黄酸负载聚(乳酸-共-乙醇酸)-大豆卵磷脂-聚乙二醇纳米粒)来靶向 CD133 和 CD44 胃癌干细胞。在这项研究中,研究了 CD44/CD133-ATRA-PLPN 对胃癌干细胞的治疗效果。这里呈现的结果证实,CD44/CD133-ATRA-PLPN 能够有效地、特异性地递送至 CD44 或 CD133 胃癌干细胞,与单靶向和非靶向纳米粒相比,对胃癌干细胞的生长抑制作用增强。据我们所知,我们首次报道了通过抗体促进纳米粒递送至两种胃癌干细胞群体。由于癌症通常包含具有多种表型的不同癌症干细胞群体,我们的双重靶向纳米粒构成了一种针对癌症内多个癌症干细胞群体的有效药物递送平台。

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