Iron plays important roles in tumor growth and metastasis, and iron depletion has become a new therapeutic strategy for iron overload cancers. Cisplatin is widely applied in the clinical therapy of various malignancies, but it has no inhibitory effect on cancer metastasis. In the present study, we found that the combination of cisplatin and iron chelator Dp44mT resulted in enhanced cell apoptosis as well as attenuated cell mobility and migration in vitro. Next, we developed a nano-carrier system to promote intracellular drug accumulation and reduce the side effects in cancer cells. Results showed that the as-synthesized nanoparticles (NPs) exhibited excellent antitumor efficiency when combined with Dp44mT. In breast tumor-bearing mice, the combination of the NPs and Dp44mT dramatically prevented orthotopic mammary tumor growth and inhibited metastasis via downregulation of VEGFα, MMP2 and Vimentin. In conclusion, as a versatile nano-platform for the combination of chemotherapy and iron chelators, the current design holds great potential for metastasis-inhibited cancer therapy.

中文翻译：

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通过靶向铁稳态，增强铂前药纳米颗粒的化学治疗功效并抑制癌症转移。

铁在肿瘤的生长和转移中起着重要的作用，而铁的消耗已经成为铁超负荷癌症的一种新的治疗策略。顺铂广泛用于各种恶性肿瘤的临床治疗，但对癌症转移没有抑制作用。在本研究中，我们发现顺铂和铁螯合剂Dp44mT的组合可增强细胞凋亡，并减弱体外细胞迁移和迁移。接下来，我们开发了一种纳米载体系统，以促进细胞内药物积累并减少癌细胞中的副作用。结果表明，与Dp44mT结合时，合成后的纳米颗粒（NPs）表现出优异的抗肿瘤功效。在带有乳腺肿瘤的小鼠中，NPs和Dp44mT的组合可通过下调VEGFα，MMP2和波形蛋白而显着地阻止原位乳腺肿瘤的生长并抑制转移。总之，作为用于化学疗法和铁螯合剂结合的多功能纳米平台，当前的设计在抑制转移的癌症治疗中具有巨大的潜力。