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Effective treatment of drug resistant recurrent breast tumors harboring cancer stem-like cells by staurosporine/epirubicin co-loaded polymeric micelles
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2017-08-24 , DOI: 10.1016/j.jconrel.2017.08.025
Juanjuan Zhang , Hiroaki Kinoh , Louise Hespel , Xueying Liu , Sabina Quader , John Martin , Tsukasa Chida , Horacio Cabral , Kazunori Kataoka

Breast cancer recurrence and resistance are associated with cancer stem-like cell (CSC) sub-populations. As conventional therapies fail to treat CSCs, institution of novel therapeutic strategies capable of eradicating both cancer cells and CSCs is central for achieving effective treatments with long-term survival. Here, we studied the ability of polymeric micelles cooperatively loading the cytotoxic drug epirubicin (Epi) and the CSC inhibitor staurosporine (STS) to treat breast tumors, particularly when tumors relapsed after chemotherapy. The STS/Epi-loaded micelles (STS/Epi/m) demonstrated potent therapeutic efficacy against both naïve orthotopic 4T1-luc breast tumors and their recurrent Epi-resistant counterparts, significantly prolonging survival. This efficacy enhancement of STS/Epi/m was correlated with the ability of the micelles to suppress the CSC-associated sub-populations of breast cancer, i.e. the aldehyde dehydrogenase-positive (ALDH+) population and the CD44+/CD24 fraction, in Epi-resistant cells and tumors. These results demonstrated STS/Epi/m as a promising strategy for effective management of breast cancer.



中文翻译:

星形孢菌素/厄比霉素共载聚合物胶束有效治疗带有癌干样细胞的耐药性复发性乳腺肿瘤

乳腺癌的复发和耐药与癌症干细胞样(CSC)亚群有关。由于常规疗法无法治疗CSC,因此能够消灭癌细胞和CSC的新型治疗策略的建立对于实现具有长期存活率的有效治疗至关重要。在这里,我们研究了聚合物胶束协同加载细胞毒性药物表柔比星(Epi)和CSC抑制剂星形孢菌素(STS)治疗乳腺肿瘤的能力,特别是当化疗后肿瘤复发时。载有STS / Epi的胶束(STS / Epi / m)对天然的原位4T1-luc乳腺肿瘤及其复发的Epi抗药性肿瘤均显示出有效的治疗功效,从而显着延长了生存期。醛脱氢酶阳性(ALDH +)人口和CD44 + / CD24 -分数,在落射抗性细胞和肿瘤。这些结果表明,STS / Epi / m是有效治疗乳腺癌的有前途的策略。

更新日期:2017-08-24
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