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 (IC50) 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.
Keywords: Apoferritin; Breast cancer; Cancer stem cells; Drug delivery; Mertansine; Nanocages.
Copyright © 2018. Published by Elsevier B.V.