Codelivery of salinomycin and docetaxel using poly(D,L-lactic-co-glycolic acid)- poly(ethylene glycol) nanoparticles to target both gastric cancer cells and cancer stem cells
Codelivery of salinomycin and docetaxel using poly(D,L-lactic-co-glycolic acid)- poly(ethylene glycol) nanoparticles to target both gastric cancer cells and cancer stem cells
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DOI：
10.1097/cad.0000000000000541
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发表时间：
2017-10-01
影响因子：
2.3
通讯作者：
Cao, Yu
中科院分区：
文献类型：
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作者：
Li, Lan;Cui, Dejun;Cao, Yu
近年来，胃癌干细胞（Cancer stem cells, CSCs）已成为胃癌成功治疗的关键靶点。越来越多的证据表明，csc和癌细胞都应该被根除，以达到最佳的治疗效果。在本研究中，盐霉素被报道可以杀死csc，与多西他赛联合使用，多西他赛是一种化疗药物，用于胃癌的一线治疗，以根除GC干细胞（SCs）和癌细胞。将盐霉素和多西他赛分别装入约140 nm的聚（D， l -乳酸-羟基乙酸）-聚乙二醇纳米颗粒中，具有粒径分布窄、载药量高、药物缓释等特点。以CD44表达为CSC表型，通过磁激活细胞分选分离GC sc。CD4(4+) GC SCs在裸鼠中表现出SCs的特征，包括SC基因表达增加、瘤球形成能力增强和致瘤性增强。我们发现，盐霉素和负载盐霉素的纳米颗粒（salinomycin- nps）都可以选择性地根除胃癌细胞，这反映在肿瘤球形成能力和CD4（4+）胃癌细胞的频率上，而多西紫杉醇和负载多西紫杉醇的纳米颗粒（docetaxel- nps）可以显著根除胃癌细胞。在移植胃癌裸鼠中，盐霉素nps和盐霉素显著减少肿瘤内胃癌SCs的数量。值得注意的是，盐碱霉素- nps联合多西他赛- nps比盐碱霉素联合多西他赛、单一盐碱霉素- nps或多西他赛- nps更有效地抑制肿瘤生长。因此，salinomycin-NPs联合docetaxel-NPs通过根除GC sc和癌细胞来治疗GC是一种很有前景的策略。版权所有2017威科集团有限公司版权所有。
Cancer stem cells (CSCs) in gastric cancer (GC) have been established recently as key therapeutic targets for the successful treatment of GC. Emerging evidence suggests that both CSCs and cancer cells should be eradicated to achieve optimal therapeutic efficacy. In the present study, salinomycin, which has been reported to kill CSCs, was used in combination with docetaxel, a chemotherapeutic drug that is used as first-line therapy in GC, to eradicate both GC stem cells (SCs) and cancer cells. Salinomycin and docetaxel were loaded separately into poly(D, L-lactic-coglycolic acid)-poly(ethylene glycol) nanoparticles of similar to 140 nm with a narrow size distribution, high drug loading, and sustained drug release. GC SCs were isolated by magnetic-activated cell sorting on the basis of CD44 expression as the CSC phenotype. CD4(4+) GC SCs showed the characteristics of CSCs, including increased SC gene expression, tumorsphere formation capacity, and tumorigenicity in nude mice. We found that both salinomycin and salinomycin-loaded nanoparticles (salinomycin-NPs) could selectively eradicate GC SCs, as reflected by reduced tumorsphere formation capacity and the frequency of CD4(4+) GC cells, whereas docetaxel and docetaxel-loaded nanoparticles (docetaxel-NPs) could significantly eradicate GC cells. In nude mice bearing GC xenografts, salinomycinNPs and salinomycin significantly decreased the intratumor population of GC SCs. Notably, salinomycin-NPs combined with docetaxel-NPs suppressed tumor growth more effectively than did salinomycin combined with docetaxel, single salinomycin-NPs, or docetaxel-NPs. Therefore, salinomycin-NPs combined with docetaxel-NPs represent a promising strategy for the treatment of GC by eradicating both GC SCs and cancer cells. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.