Cerasomal Lovastatin Nanohybrids for Efficient Inhibition of Triple-Negative Breast Cancer Stem Cells To Improve Therapeutic Efficacy
Cerasomal Lovastatin Nanohybrids for Efficient Inhibition of Triple-Negative Breast Cancer Stem Cells To Improve Therapeutic Efficacy
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Cerasomal 洛伐他汀纳米杂化物可有效抑制三阴性乳腺癌干细胞，提高治疗效果
DOI：
10.1021/acsami.8b01633
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发表时间：
2018-02-28
影响因子：
9.5
通讯作者：
Deng, Xiyun
中科院分区：
文献类型：
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作者：
Song, Liujiang;Tao, Xiaojun;Deng, Xiyun
三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，在年轻女性中风险较高，预后较差，目前没有靶向治疗。癌症干细胞（CSC）越来越被认为是治疗失败和肿瘤复发的主要原因。本文报道了将洛伐他汀（LV）包封于神经酰胺脂质体中。与游离LV相比，神经酰胺酶体包封的LV（C-LV）纳米杂化物对MDA-MB-231 CSC表现出剂量和时间依赖性的细胞毒性。此外，静脉内注射C-LV纳米杂交物导致源自皮下接种MDA-MB-231细胞的异种移植肿瘤中肿瘤尺寸以剂量依赖性方式显著减小。此外，组织病理学和/或免疫组织化学分析显示，C-LV纳米杂交显著诱导乳腺形成和细胞凋亡，并抑制异种移植肿瘤中的血管生成、CSC表型和上皮向间充质转化。最重要的是，发现C-LV纳米杂交物在抑制乳腺癌异种移植物的生长和体内干细胞特性方面比游离LV更有效。据我们所知，我们是第一个证明纳米杂交体有效抑制TNBC衍生的CSC，为TNBC治疗提供了新的选择。
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a higher risk in younger women and a poorer prognosis and without targeted therapies available currently. Cancer stem cells (CSCs) are increasingly recognized as the main cause of treatment failure and tumor recurrence. The present paper reports the encapsulation of lovastatin (LV) into cerasomes. Compared with free LV, cerasome-encapsulated LV (C-LV) nanohybrids showed cytotoxicity to MDA-MB-231 CSCs in a dose and time-dependent manner. Furthermore, intravenous injection of C-LV nanohybrids resulted in a significant tumor size reduction in a dose dependent manner in xenograft tumors derived from subcutaneous inoculation of MDA-MB-231 cells. Furthermore, histopathological and/or immunohistochemical analysis revealed that C-LV nanohybrids significantly induced mammary gland formation and apoptosis and inhibited angiogenesis, the CSC phenotype, and the epithelial-to-mesenchymal transition in xenograft tumors. Most importantly, C-LV nanohybrids were found to be more effective than free LV in inhibiting the growth of breast cancer xenografts and the sternness properties in vivo. To the best of our knowledge, ours is the first demonstration of nanohybrids for efficient inhibition of CSCs derived from TNBC, offering a new option for the TNBC treatment.