Non-triggered sequential-release liposomes enhance anti-breast cancer efficacy of STS and celastrol-based microemulsion
Non-triggered sequential-release liposomes enhance anti-breast cancer efficacy of STS and celastrol-based microemulsion
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非触发序贯释放脂质体增强STS和雷公藤红素微乳的抗乳腺癌功效
DOI：
10.1039/c8bm00796a
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发表时间：
2018-12-01
影响因子：
6.6
通讯作者：
Chen, Yan
中科院分区：
文献类型：
--
作者：
Qu, Ding;Wang, Lixiang;Chen, Yan
顺序释放其内容物的共传递系统是增强抗癌功效的有效策略。在这里，我们制造了负载有丹参酮IIA磺酸钠（STS）和雷公藤红素（CM）的小尺寸微乳液的多组分脂质体（T/CM-L），通过最初释放STS来调节肿瘤微环境，随后释放CM（及其有效负载）来根除肿瘤，从而显示出协同抗乳腺癌活性。 组织。体外研究表明，T/CM-L 诱导 MCF-7 细胞大量凋亡，表明对癌细胞具有协调的细胞毒性。一旦脂质体在肿瘤部位积累，STS首先从T/CM-L中释放出来，修复异常血管并降低成纤维细胞水平。由于微乳和脂质体的屏障，然后以中等速率卸载雷公藤红素以杀死肿瘤细胞，从而导致肿瘤尺寸缩小。此外，与单独使用雷公藤红素相比，T/CM-L 显示出降低的全身毒性。我们的工作为联合抗癌治疗提供了一种新策略，不仅在乳腺癌治疗方面具有广阔的前景，而且在其他实体瘤的治疗方面也具有广阔的前景。
A codelivery system that sequentially releases its contents is an effective strategy to enhance anticancer efficacy. Here, we fabricated multicomponent-based liposomes (T/CM-L) loaded with sodium tanshinone IIA sulfonate (STS) and a small-sized microemulsion of celastrol (CM), which shows synergistic anti-breast cancer activity through the initial release of STS for modulation of the tumor microenvironment, and subsequent release of CM (and its payloads) for eradication of tumor tissues. In vitro studies exhibited that T/CM-L induced massive apoptosis of MCF-7 cells, indicating a coordinated cytotoxicity against cancer cells. Once the liposomes had accumulated at the tumor site, STS was released from T/CM-L in the first place to repair abnormal vessels as well as to decrease the level of fibroblasts. Owing to the barriers of the microemulsion and the liposomes, the celastrol was then unloaded at a moderate rate to kill the tumor cells, which resulted in the shrinkage of the tumor size. Furthermore, T/CM-L displayed diminished systemic toxicity compared to celastrol used alone. Our work offers a novel strategy for combination anticancer treatment and holds promising potential not only for breast cancer treatment, but also for the treatment of other solid tumors.