In this study, we describe the engineering of sub‐100 nm nanomicelles (DTX‐PC NMs) derived from phosphocholine derivative of docetaxel (DTX)‐conjugated lithocholic acid (DTX‐PC) and poly(ethylene glycol)‐tethered lithocholic acid. Administration of DTX‐PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX‐TS), the FDA‐approved formulation of DTX. Unlike DTX‐TS, DTX‐PC NMs do not cause any systemic toxicity and slow the decay rate of plasma DTX concentration in rodents and non‐rodent species including non‐human primates. We further demonstrate that DTX‐PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNA methyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore, this unique system has the potential to improve the quality of life in cancer patients and can be translated as a next‐generation chemotherapeutic.

中文翻译：

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胆汁酸系多西他赛为基础的Nanomicelles通过表观遗传改变减轻肿瘤进展。

在本研究中，我们描述了从多西他赛（DTX）共轭的石胆酸（DTX-PC）和聚乙二醇乙二醇系的石胆酸的磷酸胆碱衍生物衍生的亚100 nm纳米胶束（DTX-PC NMs）的工程设计。与FDA批准的DTX制剂Taxotere（DTX-TS）相比，施用DTX-PC NM可以减缓肿瘤进展并提高小鼠的生存能力。与DTX‐TS不同，DTX‐PC NM在啮齿类动物和非啮齿类动物（包括非人类灵长类动物）中不会引起任何系统毒性，并且不会减慢血浆DTX浓度的衰减速率。我们进一步证明DTX-PC NMs通过抑制DNA甲基转移酶活性并增加Sparcl1的表达而导致Sparcl1的CpG岛（肿瘤抑制基因）脱甲基化，从而导致肿瘤消退。所以，