School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China.
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Int J Pharm. 2018 Dec 20;553(1-2):201-209. doi: 10.1016/j.ijpharm.2018.10.038. Epub 2018 Oct 16.
Cancer stem-like cells (CSCs) are proposed to be responsible for tumor metastasis, resistance and relapse after therapy, but are unable to be eliminated by many current therapies. Herein, we report that the apoferritin nanocages loading cytotoxic mertansine (M-AFN) can significantly improve their uptake in CSCs-enriched tumorspheres and effectively eradicate CSCs in tumorspheres for anticancer therapy. M-AFN were uniformly nanocage structures with the mean diameter of 11.26 ± 2.58 nm and the loading capacity of 0.62%. In the CSCs-enriched tumorsphere model, M-AFN could be preferentially internalized by tumorsphere cells and the average half-inhibitory concentration (IC) of M-AFN was obviously reduced by 5.46-fold when comparing to the parent 4T1 breast cancer cells. Moreover, both the already existing tumorspheres and the formation of secondary tumorspheres were drastically disrupted by M-AFN, but barely impacted by mertansine alone. The flow cytometer analysis showed the CSCs fractions in tumorspheres were considerably reduced by the M-AFN treatment. Therefore, the apoferritin nanocages represent an encouraging nanoplatform to eradicate CSCs for effective anticancer therapy.
肿瘤干细胞（CSCs）被认为是导致肿瘤转移、治疗后耐药和复发的原因，但许多现有疗法无法将其消除。在此，我们报告载有细胞毒性美登素（M-AFN）的脱铁转铁蛋白纳米笼能够显著提高其在富含 CSCs 的肿瘤球中的摄取，并有效地消除肿瘤球中的 CSCs 以进行抗癌治疗。M-AFN 具有均匀的纳米笼结构，平均直径为 11.26±2.58nm，载药量为 0.62%。在富含 CSCs 的肿瘤球模型中，M-AFN 可优先被肿瘤球细胞内化，与亲本 4T1 乳腺癌细胞相比，M-AFN 的平均半抑制浓度（IC）明显降低了 5.46 倍。此外，M-AFN 可明显破坏已存在的肿瘤球和次级肿瘤球的形成，而美登素单独作用几乎没有影响。流式细胞仪分析显示，M-AFN 处理后肿瘤球中的 CSCs 分数明显减少。因此，脱铁转铁蛋白纳米笼为有效抗癌治疗消除 CSCs 提供了一种有前途的纳米平台。
