The Clinical Potential of Targeted Nanomedicine: Delivering to Cancer Stem-like Cells
The Clinical Potential of Targeted Nanomedicine: Delivering to Cancer Stem-like Cells
复制标题
DOI：
10.1038/mt.2013.231
复制
发表时间：
2014-02-01
影响因子：
12.4
通讯作者：
Chang, Esther H.
中科院分区：
文献类型：
--
作者：
Kim, Sang-Soo;Rait, Antonina;Chang, Esther H.
癌症干细胞（CSCs）与许多人类癌症的复发和治疗耐药有关。因此，针对csc的药物递送策略是开发更有效的抗癌治疗的理想方法。我们已经开发了一种肿瘤靶向纳米给药平台（scL），用于分子药物的全身给药。在使用携带各种有效载荷的scL纳米复合物治疗后，我们在许多动物模型中观察到精细的肿瘤靶向特异性和显著的抗肿瘤反应，并具有长期生存益处。我们假设这种观察到的疗效可能归因于，至少部分归因于CSCs的消除。在这里，我们在各种小鼠模型中证明了scL靶向CSCs和分化的非干细胞（non-CSCs）的能力，包括皮下和颅内异种移植、同基因和化学诱导的肿瘤。我们还发现，全身给药携带wtp53基因的scL能够诱导皮下结直肠癌异种移植物中CSCs和非CSCs的肿瘤生长抑制和死亡，这表明这可能是减少癌症复发和治疗抵抗的有效方法。这种scL纳米复合物正在许多临床试验中进行评估，在这些试验中，它已被证明具有良好的耐受性和抗癌活性。
Cancer stem-like cells (CSCs) have been implicated in recurrence and treatment resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to eliminate CSCs is a desirable approach for developing a more effective anticancer therapy. We have developed a tumor-targeting nanodelivery platform (scL) for systemic administration of molecular medicines. Following treatment with the scL nanocomplex carrying various payloads, we have observed exquisite tumor-targeting specificity and significant antitumor response with longterm survival benefit in numerous animal models. We hypothesized that this observed efficacy might be attributed, at least in part, to elimination of CSCs. Here, we demonstrate the ability of scL to target both CSCs and differentiated nonstem cancer cells (non-CSCs) in various mouse models including subcutaneous and intracranial xenografts, syngeneic, and chemically induced tumors. We also show that systemic administration of scL carrying the wtp53 gene was able to induce tumor growth inhibition and the death of both CSCs and nonCSCs in subcutaneous colorectal cancer xenografts suggesting that this could be an effective method to reduce cancer recurrence and treatment resistance. This scL nanoconnplex is being evaluated in a number of clinical trials where it has been shown to be well tolerated with indications of anticancer activity.