National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.
J Mater Chem B. 2019 Oct 16;7(40):6075-6086. doi: 10.1039/c9tb01093a.
The residual tumor cells after chemotherapy, even in very small numbers, are generally drug-resistant and invasive, which might result in the progress of tumor metastasis and recurrence. In this research, a new combination chemotherapy strategy of salinomycin (SL) that could selectively inhibit multidrug-resistant tumor cells and a traditional broad-spectrum antitumor drug, doxorubicin (DOX), based on redox-degradable nano-micelles was developed to overcome drug resistance in vitro. The results in vitro indicated that DOX + SL co-loaded nano-micelles could not only escape from the drug efflux of adriamycin-resistant MCF-7 cells (A/MCF-7) but also penetrated and infiltrated into 3D-cultured MCF-7 and 4T1 tumor spheres in vitro more effectively, resulting in a strong antiproliferative effect. In the allogeneic metastatic 4T1 tumor model, the combination chemotherapy of DOX + SL encapsulated in nano-micelles effectively suppressed tumor growth with no splenomegaly and no other major tissue damage, and reversed the EMT progress, and inhibited tumor recurrence and metastasis more effectively after drug withdrawal.
化疗后残留的肿瘤细胞，即使数量非常少，通常也具有耐药性和侵袭性，这可能导致肿瘤转移和复发的进展。在这项研究中，开发了一种新的组合化疗策略，即利用基于氧化还原降解的纳米胶束将能够选择性抑制多药耐药肿瘤细胞的药物盐霉素 (SL) 与传统的广谱抗肿瘤药物阿霉素 (DOX) 联合使用，以克服体外的耐药性。体外实验结果表明，DOX+SL 共载纳米胶束不仅可以逃避阿霉素耐药 MCF-7 细胞（A/MCF-7）的药物外排，而且还可以更有效地穿透和渗透到体外培养的 MCF-7 和 4T1 肿瘤球体中，从而产生强烈的抗增殖作用。在同种异体转移性 4T1 肿瘤模型中，载有 DOX+SL 的纳米胶束的联合化疗有效抑制了肿瘤生长，没有脾肿大和其他主要组织损伤，并且逆转了 EMT 进展，在停药后更有效地抑制了肿瘤的复发和转移。
