Nanshan District Key Lab for Biopolymers and Safety Evaluation, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, P. R. China.
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Nanoscale Horiz. 2020 Jun 2;5(6):999-1015. doi: 10.1039/d0nh00148a.
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.
铁在肿瘤生长和转移中起着重要作用，铁耗竭已成为治疗铁过载癌症的一种新策略。顺铂广泛应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，我们发现顺铂与铁螯合剂 Dp44mT 联合使用可增强细胞凋亡，并减弱体外细胞迁移和迁移能力。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降低癌细胞的副作用。结果表明，合成的纳米粒子（NPs）与 Dp44mT 联合使用时表现出优异的抗肿瘤效率。在乳腺癌荷瘤小鼠中，NPs 与 Dp44mT 的联合使用通过下调 VEGFα、MMP2 和波形蛋白，显著抑制了原位乳腺肿瘤的生长并抑制了转移。总之，作为化疗药物和铁螯合剂联合使用的多功能纳米平台，该设计在抑制转移的癌症治疗方面具有巨大的潜力。
