The CD44 receptor is common among many cancer types where overexpression is synonymous with poor prognosis in prostate, glioma, and breast cancer. More notably CD44 overexpression has been shown in a number of different cancer stem cells (CSC) which are present in many solid tumors and drive growth, recurrence, and resistance to conventional therapies. Triple negative breast cancer CSCs correlate to worse prognosis and early relapse due to higher drug resistance and increased tumor heterogeneity and thus are prime targets for anticancer therapy. To specifically target cells overexpressing CD44 receptors, including CSCs, we synthesized a pentameric nanocomplex (PNC) containing gold nanoparticles, doxorubicin (Dox) conjugated to thiolated hyaluronic acid via an acid-labile hydrazone bond, and thiolated poly(ethylene glycol) DNA CD44 aptamer. In vitro drug release was highest at 8 h time point at acidic pH (pH 4.7) and in 10 mM glutathione. The PNC is almost an order of magnitude more effective than Dox alone in CD44+ cells versus CD44 low cells. Functionally, the PNC reduced CSC self-renewal. The PNC provides a therapeutic strategy that can improve the efficiency of Dox and decrease nontargeted toxicity thereby prolonging its use to individual patients.

中文翻译：

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五部分五聚体纳米复合物显示多柔比星在 CD44+ 癌细胞中的功效得到改善

CD44 受体在许多癌症类型中很常见，其中过度表达与前列腺癌、神经胶质瘤和乳腺癌的不良预后同义。更值得注意的是，CD44 过度表达已在许多不同的癌症干细胞 (CSC) 中显示出来，这些细胞存在于许多实体瘤中，并促进生长、复发和对常规疗法的耐药性。由于较高的耐药性和肿瘤异质性增加，三阴性乳腺癌 CSC 与较差的预后和早期复发相关，因此是抗癌治疗的主要目标。为了特异性靶向过度表达 CD44 受体的细胞（包括 CSC），我们合成了五聚体纳米复合物 (PNC)，其中含有金纳米颗粒、通过酸不稳定腙键与硫醇化透明质酸缀合的阿霉素 (Dox)，以及硫醇化聚乙二醇 DNA CD44 适体。在酸性 pH 值（pH 4.7）和 10 mM 谷胱甘肽中，体外药物释放在 8 小时时间点最高。与 CD44 低细胞相比，PNC 在 CD44+ 细胞中比单独使用 Dox 更有效一个数量级。从功能上讲，PNC 减少了 CSC 的自我更新。PNC 提供了一种治疗策略，可以提高 Dox 的效率并减少非靶向毒性，从而延长其对个体患者的使用。