As a result of their ability to transform into bulk cancer cells and their resistance to radiotherapy and chemotherapy, cancer stem cells (CSCs) are currently considered as a major obstacle for cancer treatment. Application of multiple drugs using nanocarriers is a promising approach to simultaneously eliminate noncancer stem cells (non-CSCs) and CSCs. Herein, to employ the advantages of nanomedicine while avoiding new excipients, pH-responsive prodrug (PEG–CH═N–DOX) was employed as the surfactant to fabricate cargo-free nanomedicine for codelivery of DOX conjugated prodrug with SN38 to synergistically eradicate breast cancer stem cells (bCSCs) and non-bCSCs. Through the intermolecular interaction between DOX and SN38, PEG–CH═N–DOX and SN38 were assembled together to form a stable nanomedicine. This nanomedicine not only dramatically enhanced drug accumulation efficiency at the tumor site but also effectively eliminated bCSCs and non-bCSCs, which resulted in achieving a superior in vivo tumor inhibition activity. Additionally, the biosafety of this nanomedicine was systematically studied through immunohistochemistry, blood biochemistry assay, blood routine examination, and metabolomics. The results revealed that this nanomedicine significantly reduced the adverse effects of DOX and SN38. Therefore, this simple yet efficient nanomedicine provided a promising strategy for future clinical applications.

中文翻译：

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具有pH敏感性的无货物纳米药物，用于协同消灭乳腺癌干细胞与SN38的DOX结合前药。

由于它们具有转化成大量癌细胞的能力以及对放射疗法和化学疗法的抗性，因此目前认为癌症干细胞（CSC）是癌症治疗的主要障碍。使用纳米载体的多种药物的应用是同时消除非癌干细胞（non-CSCs）和CSCs的一种有前途的方法。在本文中，为了利用纳米药物的优势而又避免了新的赋形剂，采用了pH响应前药（PEG-CH═N-DOX）作为表面活性剂来制备无货物的纳米药物，以将DOX结合前药与SN38进行代码传递，从而协同消除乳腺癌。干细胞（bCSC）和非bCSC。通过DOX和SN38之间的分子间相互作用，PEG-CH═N-DOX和SN38组装在一起形成稳定的纳米药物。这种纳米药物不仅显着提高了肿瘤部位的药物蓄积效率，而且还有效消除了bCSCs和非bCSCs，从而获得了优异的体内肿瘤抑制活性。此外，通过免疫组织化学，血液生化分析，血液常规检查和代谢组学系统地研究了这种纳米药物的生物安全性。结果表明，这种纳米药物显着降低了DOX和SN38的不良反应。因此，这种简单而有效的纳米药物为未来的临床应用提供了有希望的策略。通过免疫组织化学，血液生化分析，血液常规检查和代谢组学系统地研究了这种纳米药物的生物安全性。结果表明，这种纳米药物显着降低了DOX和SN38的不良反应。因此，这种简单而有效的纳米药物为未来的临床应用提供了有希望的策略。通过免疫组织化学，血液生化分析，血液常规检查和代谢组学系统地研究了这种纳米药物的生物安全性。结果表明，这种纳米药物显着降低了DOX和SN38的不良反应。因此，这种简单而有效的纳米药物为未来的临床应用提供了有希望的策略。