The clinical application of the cytotoxic chemotherapeutic agents in the treatment of metastatic breast cancer is limited by their poor selectivity to cancer cells. In this work, a bionic nanodevice consisting of the docetaxel (DTX)‐heparan sulfate (HS) conjugate (HS‐DTX) micelle with a red blood cells membrane (RBC) coating on its surface, termed as rHS‐DTX, is first constructed. It is found that the cytotoxicity of DTX is concealed by HS in human mammary epithelial Michigan Cancer Foundation (MCF)‐10A cells but restored in human mammary cancer MCF‐7 cells because HS is hydrolyzed by heparanase (Hpa), which is overexpressed only in MCF‐7 but not MCF‐10A cells. The RBC coating enhances the cellular uptake of HS‐DTX and endows it with the long circulating ability in blood. In the MCF‐7 metastatic breast cancer mice model, rHS‐DTX exhibits 6.35‐fold higher intratumor DTX accumulation than the free DTX injection and achieves a tumor inhibiting rate of 98.2% and a lung metastasis suppression rate of 99.6%. No severe toxicity is observed in the major organs and blood of mice treated with rHS‐DTX. In summary, rHS‐DTX can provide a promising strategy for targeting therapy of metastatic breast cancer by improving the tumor‐suppressing efficacy of DTX.

中文翻译：

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利用肝素酶的肿瘤细胞选择性仿生纳米器件可对抗转移性乳腺癌。

细胞毒性化学治疗剂在治疗转移性乳腺癌中的临床应用受到其对癌细胞选择性差的限制。在这项工作中，首先构建了由多西他赛（DTX）-硫酸乙酰肝素（HS）共轭物（HS-DTX）胶束组成，表面具有红细胞膜（RBC）涂层的仿生纳米器件，称为rHS-DTX。 。发现在人类乳腺上皮密歇根癌症基金会（MCF）-10A细胞中HS掩盖了DTX的细胞毒性，但在人类乳腺MCF-7细胞中恢复了DTX的细胞毒性，因为HS被乙酰肝素酶（Hpa）水解，而乙酰肝素酶仅在Hpa中过表达。 MCF-7，但不是MCF-10A电池。RBC涂层增强了HS‐DTX对细胞的吸收，并赋予其在血液中的长循环能力。在MCF-7转移性乳腺癌小鼠模型中，rHS-DTX展示为6。肿瘤内DTX的蓄积比免费DTX注射高35倍，肿瘤抑制率达到98.2％，肺转移抑制率达到99.6％。用rHS-DTX处理的​​小鼠的主要器官和血液中未观察到严重毒性。总之，rHS‐DTX可通过提高DTX的抑瘤功效，为转移性乳腺癌的靶向治疗提供有希望的策略。