2022-11-27

Nanomedicines Eradicating Cancer Stem-like Cells in Vivo by pH-Triggered Intracellular Cooperative Action of Loaded Drugs

image.png

ABSTRACT: Nanomedicines capable of control over drug functions have potential for developing resilient therapies, even against tumors harboring recalcitrant cancer stem cells (CSCs).
能够控制药物功能的纳米药物具有开发弹性疗法的潜力，甚至可以针对含有顽固性癌症干细胞（CSC）的肿瘤。

By coordinating drug interactions within the confined inner compartment of core−shell nanomedicines, we conceived multicomponent nanomedicines directed to achieve synchronized and synergistic drug cooperation within tumor cells as a strategy for enhancing efficacy, overcoming drug resistance, and eradicating CSCs.
通过协调核壳纳米药物有限空间内的药物相互作用，作者设计了多组分纳米药物，旨在实现肿瘤细胞内的同步和协同药物合作，以期成为提高疗效、克服耐药性和根除CSCs的策略。

The approach was validated by using polymeric micellar nanomedicines co-incorporating the pan-kinase inhibitor staurosporine (STS), which was identified as the most potent CSC inhibitor from a panel of signaling-pathway inhibitors, and the cytotoxic agent epirubicin (Epi), through rationally contriving the affinity between the drugs.
该方法通过使用聚合胶束纳米药物与泛激酶抑制剂星形孢菌素（STS）和细胞毒性剂表柔比星（Epi）共同结合，前者被确定为一组信号通路抑制剂中最有效的CSC抑制剂，通过合理地计算药物之间的亲和力，验证了该方法。

The micelles released both drugs simultaneously, triggered by acidic endosomal pH, attaining concurrent intracellular delivery, with STS working as a companion for Epi, down-regulating efflux transporters and resistance mechanisms induced by Epi.
胶束同时释放两种药物，由酸性内体pH触发，实现并发细胞内递送，STS作为Epi的伴侣，下调外排转运蛋白和Epi诱导的抗性机制。

These features prompted the nanomedicines to eradicate orthotopic xenografts of Epi-resistant mesothelioma bearing a CSC subpopulation.
这些特征促进纳米药物根除携带CSC亚群的表柔比星耐药间皮瘤的原位异种移植物。

DOI: 10.1021/acsnano.6b00900 ACS Nano 2016, 10, 5643−5655