Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo
Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo
复制标题
使用 CD44 配体包被的纳米粒子在体外和体内选择性杀死表达活化 CD44 的乳腺癌细胞
DOI：
10.18632/oncotarget.3681
复制
发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Gao Feng
中科院分区：
文献类型：
--
作者：
Yang Cuixia;He Yiqing;Zhang Huizhen;Liu Yiwen;Wang Wenjuan;Du Yan;Gao Feng
细胞表面糖蛋白CD44在癌细胞中表达，并已在临床前研究中用作治疗靶点。然而，CD44在包括造血细胞在内的多种细胞类型中的普遍表达阻碍了其在靶向治疗中的应用。在这里，我们证明了CD44在乳腺癌细胞上被激活，但在体外和体内正常细胞上无活性。我们分析了34例临床原发性乳腺癌和正常乳腺组织，证明CD44在乳腺癌细胞上处于活性状态，而在正常细胞上处于非活性状态。此外，基于CD44与其配体透明质酸（HA）的结合特性，我们自组装HA涂层纳米粒并研究其选择性靶向功效。我们的研究结果表明，HA包被的纳米粒子携带的CD44配体选择性靶向癌细胞在体外和体内，杀死乳腺癌细胞，而保留正常细胞。我们的研究表明，CD44的活性状态在乳腺癌细胞的选择性靶向中起着至关重要的作用，通过避免对CD44静止的正常细胞的非特异性毒性。这些发现可能为在人类其他癌症中选择性靶向癌细胞提供新的思路。
The cell surface glycoprotein CD44 is expressed in cancer cells and has been used as a therapeutic target in preclinical studies. However, the ubiquitous expression of CD44 in numerous cell types, including hematopoietic cells, has hindered its application in targeted therapy. Here, we demonstrated that CD44 was activated on breast cancer cells but was inactive on normal cells in vitro and in vivo. We analyzed 34 clinical primary tumor and normal breast tissues and demonstrated that CD44 was in an active state on breast cancer cells but in an inactive state on normal cells. Furthermore, based on the binding property of CD44 with its ligand hyaluronan (HA), we self-assembled HA-coated nanoparticles and studied their selective targeting efficacy. Our results indicate that HA-coated nanoparticles bearing the CD44 ligand selectively targeted cancer cells both in vitro and in vivo, killing breast cancer cells while sparing normal cells. Our study suggested that the active state of CD44 plays a crucial role in the selective targeting of breast cancer cells by avoiding nonspecific toxicity to CD44-quiescent normal cells. These findings may provide a new idea for the selective targeting of cancer cells in other human cancers.
登录
查看更多内容
影响因子：
11.5
作者：
Tijink, Bernard M.;Buter, Jan;van Dongen, Guus A. M. S.
通讯作者：
van Dongen, Guus A. M. S.
影响因子：
5.2
作者：
A. Sauter;C. Kloft;S. Gronau;F. Bogeschdorfer;T. Erhardt;W. Golze;C. Schroen;A. Staab;H. Riechelmann;K. Hoermann
通讯作者：
A. Sauter;C. Kloft;S. Gronau;F. Bogeschdorfer;T. Erhardt;W. Golze;C. Schroen;A. Staab;H. Riechelmann;K. Hoermann
DOI：
10.1172/jci2494
发表时间：
1998-09
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
J. Moll;Sophia K. Khaldoyanidi;Jonathan P. Sleeman;M. Achtnich;I. Preuss;H. Ponta;P. Herrlich
通讯作者：
J. Moll;Sophia K. Khaldoyanidi;Jonathan P. Sleeman;M. Achtnich;I. Preuss;H. Ponta;P. Herrlich
影响因子：
14
作者：
Cuixia Yang;Yi-wen Liu;Yi-qing He;Yan Du;Wen-juan Wang;Xiaoxin Shi;F. Gao
通讯作者：
Cuixia Yang;Yi-wen Liu;Yi-qing He;Yan Du;Wen-juan Wang;Xiaoxin Shi;F. Gao
影响因子：
5.2
作者：
Klingbeil, Pamela;Marhaba, Rachid;Zoeller, Margot
通讯作者：
Zoeller, Margot