Mol Pharm. 2018 Aug 6;15(8):3343-3355. doi: 10.1021/acs.molpharmaceut.8b00367. Epub 2018 Jul 6.
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.
由于其能够转化为大量癌细胞以及对放疗和化疗的抗性，癌症干细胞 (CSC) 目前被认为是癌症治疗的主要障碍。使用纳米载体应用多种药物是同时消除非癌症干细胞 (非 CSC) 和 CSC 的一种有前途的方法。在此，为了利用纳米医学的优势，同时避免使用新的赋形剂，将 pH 响应性前药 (PEG-CH═N-DOX) 用作表面活性剂，以制备无载药的纳米药物，用于共递送与 SN38 缀合的 DOX，以协同根除乳腺癌干细胞 (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。这种纳米药物不仅极大地提高了肿瘤部位的药物积累效率，而且有效地消除了 bCSC 和非 bCSC，从而实现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，这种纳米药物显著降低了 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前途的策略。
