由于对传统化疗的耐药性，局部晚期和转移性三阴性乳腺癌（TNBC）的治疗管理通常受到限制。超过 90% 的乳腺癌相关死亡率是由转移造成的；因此，预防或靶向转移的临床需求是巨大的。癌症干细胞（CSC）的上皮间质转化（EMT）是转移的关键决定因素。阿霉素（DOX）是常用的针对 TNBC 的化疗药物，可能会增加患者转移的风险。癌症治疗后，具有EMT特征的CSC持续存在，这有助于晚期恶性肿瘤和癌症复发。医学应用纳米技术的最新发展提高了使用纳米药物靶向这些 CSC 的可能性。因此，我们提出了一种 DOX 与膳食吲哚 3,3'-二吲哚甲烷 (DIM) 组合治疗的新方法，这是一个有趣的研究领域，可能针对 TNBC 中 CSC 介导的 EMT 诱导。为了将这两种化合物有效递送至肿瘤微环境，基于介孔二氧化硅纳米颗粒包裹的外泌体的先进药物递送方法可能提供一种有吸引力的策略。根据我们的研究结果，DOX能够诱导CSC中的EMT，从而使乳腺癌发生细胞更具侵袭性和转移性。在由 MDAMB-231 和 4T1 球体产生的 CSC 中，N-钙粘蛋白、Snail、Slug 和 Vimentin 的过度表达以及 DOX 治疗对 E-钙粘蛋白的下调，不仅证明了 EMT 诱导，而且强调了对新型化疗药物的迫切需要组合来抵消 DOX 的这种有害作用。为了实现这一目标，DIM 与 DOX 结合，并通过将它们装载到封装在外泌体中的介孔二氧化硅纳米粒子 (e-DDMSNP) 中，同时递送至 CSC。这些外泌体提高了 DIM 和 DOX 在体外和体内 CSC 生态位中的特异性、稳定性和更好的归巢能力。此外，用 e-DDMSNP 处理富含 CSC 的 TNBC 细胞群后，观察到 DOX 介导的 EMT 诱导显着减少。我们的研究旨在通过引入这种独特的针对 CSC 诱导的 EMT 的外泌体纳米制剂，提出治疗 TNBC 的新概念.© 2024。作者。

Therapeutic management of locally advanced and metastatic triple negative breast cancer (TNBC) is often limited due to resistance to conventional chemotherapy. Metastasis is responsible for more than 90% of breast cancer-associated mortality; therefore, the clinical need to prevent or target metastasis is immense. The epithelial to mesenchymal transition (EMT) of cancer stem cells (CSCs) is a crucial determinant in metastasis. Doxorubicin (DOX) is the frequently used chemotherapeutic drug against TNBC that may increase the risk of metastasis in patients. After cancer treatment, CSCs with the EMT characteristic persist, which contributes to advanced malignancy and cancer recurrence. The latest developments in nanotechnology for medicinal applications have raised the possibility of using nanomedicines to target these CSCs. Hence, we present a novel approach of combinatorial treatment of DOX with dietary indole 3,3'-diindolylmethane (DIM) which is an intriguing field of research that may target CSC mediated EMT induction in TNBC. For efficient delivery of both the compounds to the tumor niche, advance method of drug delivery based on exosomes sheathed with mesoporous silica nanoparticles may provide an attractive strategy.DOX, according to our findings, was able to induce EMT in CSCs, making the breast cancer cells more aggressive and metastatic. In CSCs produced from spheres of MDAMB-231 and 4T1, overexpression of N-cadherin, Snail, Slug, and Vimentin as well as downregulation of E-cadherin by DOX treatment not only demonstrated EMT induction but also underscored the pressing need for a novel chemotherapeutic combination to counteract this detrimental effect of DOX. To reach this goal, DIM was combined with DOX and delivered to the CSCs concomitantly by loading them in mesoporous silica nanoparticles encapsulated in exosomes (e-DDMSNP). These exosomes improved the specificity, stability and better homing ability of DIM and DOX in the in vitro and in vivo CSC niche. Furthermore, after treating the CSC-enriched TNBC cell population with e-DDMSNP, a notable decrease in DOX mediated EMT induction was observed.Our research seeks to propose a new notion for treating TNBC by introducing this unique exosomal nano-preparation against CSC induced EMT.© 2024. The Author(s).