Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells
Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells
复制标题
全反式视黄酸和阿霉素联合递送用于癌症治疗并协同抑制癌症干细胞
DOI：
10.1016/j.biomaterials.2014.10.018
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发表时间：
2015-01-01
期刊：
影响因子：
14
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Sun, Rong;Liu, Yang;Wang, Jun
通过同时递送两种或更多种药物与纳米颗粒的组合治疗已被证明是用于癌症治疗的优雅且有效的方法。在本文中，我们采用联合疗法来消除大量肿瘤细胞和具有高自我更新能力并在癌症治疗失败中起关键作用的罕见癌症干细胞（CSC）。全反式维甲酸（ATRA）是一种强大的肿瘤干细胞分化剂，临床上广泛使用的化疗药物阿霉素（DOX）通过单一乳液方法同时包封在同一纳米颗粒中。已经证明，基于ATRA和DOX同时递送的治疗可以有效地将药物递送到非CSC和CSC以分化和杀死癌细胞。CSC分化为非CSC可以降低其自我更新能力并增加其对化疗的敏感性;通过联合治疗，证明了显着改善的抗癌效果。这种组合药物递送系统的施用可以显著增加药物在肿瘤组织和癌症干细胞中的富集，极大地增强对肿瘤生长的抑制，同时以协同方式降低CSC的发生率。(C)2014爱思唯尔有限公司版权所有。
Combination treatment through simultaneous delivery of two or more drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employ a combination therapy for eliminating both the bulk tumor cells and the rare cancer stem cells (CSCs) that have a high self-renewal capacity and play a critical role in cancer treatment failure. All-trans-retinoic acid (ATRA), a powerful differentiation agent of cancer stem cells and the clinically widely used chemotherapy agent doxorubicin (DOX) are simultaneously encapsulated in the same nanoparticle by a single emulsion method. It is demonstrated that ATRA and DOX simultaneous delivery-based therapy can efficiently deliver the drugs to both non-CSCs and CSCs to differentiate and kill the cancer cells. Differentiation of CSCs into non-CSCs can reduce their self-renewal capacity and increase their sensitivity to chemotherapy; with the combined therapy, a significantly improved anti-cancer effect is demonstrated. Administration of this combinational drug delivery system can markedly augment the enrichment of drugs both in tumor tissues and cancer stem cells, prodigiously enhancing the suppression of tumor growth while reduce the incidence of CSC in a synergistic manner. (C) 2014 Elsevier Ltd. All rights reserved.