Enhanced anti-tumor and anti-metastasis therapy for triple negative breast cancer by CD44 receptor-targeted hybrid self-delivery micelles.
Enhanced anti-tumor and anti-metastasis therapy for triple negative breast cancer by CD44 receptor-targeted hybrid self-delivery micelles.
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DOI：
10.1016/j.ijpharm.2020.119085
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发表时间：
2020-01
影响因子：
5.8
通讯作者：
Yiliang Yang;Yang Long;Yashi Wang;Kebai Ren;Man Li;Zhirong Zhang;B. Xiang;Qin He
中科院分区：
文献类型：
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作者：
Yiliang Yang;Yang Long;Yashi Wang;Kebai Ren;Man Li;Zhirong Zhang;B. Xiang;Qin He
肿瘤的生长和转移是一个多步骤的过程，受多种信号通路的调控。癌症的成功治疗在很大程度上取决于抑制转移过程的能力。多相转移抑制是一种有前途的方法。本研究将透明质酸-d-α-生育酚琥珀酸酯（HA-TOS，HT）与低分子肝素-TOS（LMWH-TOS，LT）混合，形成稳定的杂化胶束（HT-LT），包裹化疗药物阿霉素（DOX），构建了一种靶向给药系统。制备的HT-LT纳米粒粒径约为125 nm，具有较高的药物包封率和持续释药行为。我们使用4 T1模型证实了HT-LT NP在体外和体内均表现出有效的靶向能力，这归因于HA与CD 44受体的结合。此外，HT-LT NPs作用于侵袭转移级联反应的不同阶段，抑制肿瘤细胞的迁移和侵袭，从而抑制肿瘤转移。这种组合策略为三阴性乳腺癌治疗提供了一种替代方法。
Tumor growth and metastasis are multistep processes regulated by multiple signaling pathways. The successful treatment of cancer largely depends on the ability to inhibit metastatic process. Multiphase inhibition of metastasis is a promising approach. Here, we described a targeting delivery system which was constructed by mixing hyaluronic acid-d-α-tocopheryl succinate (HA-TOS, HT) and low molecular weight heparin-TOS (LMWH-TOS, LT) to form a stable hybrid micelle (HT-LT), encapsulating chemotherapeutic drug doxorubicin (DOX). The prepared HT-LT NPs was about 125 nm in diameter with high drug encapsulation rate and continuous drug release behavior. We confirmed that HT-LT NPs exhibited an effective targeting ability both in vitro and in vivo using a 4T1 model that was attributed to HA binding to CD44 receptors. In addition, HT-LT NPs acted on different phases of the invasion-metastasis cascade and inhibited tumor cell migration and invasion, thus inhibiting tumor metastasis. This combinatorial strategy provided an alternative approach for triple negative breast cancer therapy.