期刊
BIOMATERIALS
卷 37, 期 -, 页码 405-414出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.10.018
关键词
Cancer stem cell; All-trans-retinoic acid; Doxorubicin; Combination therapy; Co-delivery
资金
- National Basic Research Program of China [2010CB934001, 2013CB933900, 2012CB932500]
- National Natural Science Foundation of China [31470965, 51125012, 51390482]
- State Key Laboratory of Supramolecular Structure and Materials [sklssm201413]
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.
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