The potency of polymeric micelle-based doxorubicin, SP1049C, against cancer stem cells (CSCs) in triple negative breast cancer (TNBC) is evaluated. CSCs with high epithelial specific antigen (ESA), high CD44 and low CD24 expression levels were derived from the TNBC cancer cells, MDA-MB-231 and MDA-MB-468. These CSCs were resistant to free doxorubicin (Dox) and displayed increased colony formation, migration, and invasion in vitro, along with higher tumorigenicity in vivo, compared to the parental and non-CSCs counterparts. SP1049C downregulated the expression and inhibited the functional activity of the breast cancer resistance protein (BCRP/ABCG2) in CSCs. The polymeric micelle drug had higher cytotoxicity and potency in reducing the colony formation of CSCs compared to the free drug. It was also more potent in inhibiting the tumor growth in the orthotopic animal tumor models derived from CSCs. These results indicate that SP1049C is active against CSCs and has potential in treating TNBC.

中文翻译：

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使用阿霉素/普朗尼克聚合胶束根除三阴性乳腺癌中的癌症干细胞。

评估了基于聚合胶束的阿霉素 SP1049C 在三阴性乳腺癌 (TNBC) 中对癌症干细胞 (CSC) 的效力。具有高上皮特异性抗原 (ESA)、高 CD44 和低 CD24 表达水平的 CSC 来源于 TNBC 癌细胞 MDA-MB-231 和 MDA-MB-468。与亲本和非 CSC 对应物相比，这些 CSC 对游离多柔比星 (Dox) 具有抗性，并且在体外显示出增加的集落形成、迁移和侵袭，以及在体内更高的致瘤性。SP1049C 下调乳腺癌抗性蛋白 (BCRP/ABCG2) 在 CSCs 中的表达并抑制其功能活性。与游离药物相比，聚合物胶束药物具有更高的细胞毒性和减少 CSC 集落形成的效力。它在抑制源自 CSC 的原位动物肿瘤模型中的肿瘤生长方面也更有效。这些结果表明 SP1049C 对 CSC 具有活性，并具有治疗 TNBC 的潜力。