Nanoparticle mediated targeting of VEGFR and cancer stem cells for cancer therapy.
Nanoparticle mediated targeting of VEGFR and cancer stem cells for cancer therapy.
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DOI：
10.1186/2045-824x-3-26
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发表时间：
2011-11-14
期刊：
影响因子：
--
通讯作者：
Kumar P
中科院分区：
文献类型：
--
作者：
Ambasta RK;Sharma A;Kumar P
血管生成是肿瘤发病机制中的关键过程，因为它为恶性细胞提供营养和氧气。众所周知，肿瘤细胞分泌各种生长因子，包括VEGF，其触发内皮细胞形成新的毛细血管。防止新血管网络的扩张导致肿瘤尺寸减小和转移。VEGF的产生由缺氧通过HIF-1α对VEGF基因的转录激活来驱动。现在人们知道肿瘤含有不同类型的细胞，而癌症干细胞保留了驱动肿瘤生长的能力。它们被称为癌症干细胞，因为就像身体正常组织中存在的干细胞一样，它们可以自我更新和分化。这些癌症干细胞是癌症复发的原因，因为它们被发现对传统的癌症治疗模式如化疗和放疗具有抗性。在这篇综述中，提出了一种新的治疗癌症的模式，即利用孪生纳米粒子靶向肿瘤干细胞龛中的内皮细胞。在这篇综述中讨论的纳米颗粒，是一个双纳米颗粒的铁涂层与金，它的目标是VEGF阳性细胞附近的癌症干细胞。在孪生纳米颗粒中，一个颗粒将识别癌症干细胞，另一个缀合的纳米颗粒将识别VEGF阳性细胞，从而抑制癌症干细胞附近的内皮细胞。这种新的策略将抑制癌干细胞附近的血管生成，因此新肿瘤不能生长，旧肿瘤将无法转移。
Angiogenesis is a crucial process in tumor pathogenesis as it sustains malignant cells with nutrients and oxygen. It is well known that tumor cells secrete various growth factors, including VEGF, which triggers endothelial cells to form new capillaries. Prevention of expansion of new blood vessel networks results in reduced tumor size and metastasis. Production of VEGF is driven by hypoxia via transcriptional activation of the VEGF gene by HIF-1α. Tumours are now understood to contain different types of cells, and it is the cancer stem cells that retain the ability to drive the tumour's growth. They are called cancer stem cells because, like stem cells present in normal tissues of the body, they can self-renew and differentiate. These cancer stem cells are responsible for the relapse of cancer as they are found to be resistant to conventional modes of cancer therapy like chemotherapy and radiation. In this review, a novel mode of treatment of cancer is proposed, which utilizes the twin nanoparticle to target endothelial cells in the niche of cancer stem cell. The nanoparticle discussed in this review, is a twin nanoparticle of iron coated with gold, which targets VEGF positive cell in the vicinity of cancer stem cell. In the twin nanoparticle, one particle will recognize cancer stem cell, and another conjugated nanoparticle will recognize VEGF positive cells, thereby inhibiting endothelial cells in the proximity of cancer stem cell. This novel strategy will inhibit angiogenesis near cancer stem cell hence new tumour cannot grow and old tumour will be unable to metastasize.