Octreotide-modified liposomes containing daunorubicin and dihydroartemisinin for treatment of invasive breast cancer
Octreotide-modified liposomes containing daunorubicin and dihydroartemisinin for treatment of invasive breast cancer
复制标题
含有柔红霉素和双氢青蒿素的奥曲肽修饰脂质体用于治疗浸润性乳腺癌
DOI：
10.1080/21691401.2018.1433187
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发表时间：
2018-01-01
影响因子：
5.8
通讯作者：
Li, Xue-Tao
中科院分区：
文献类型：
--
作者：
Ju, Rui-Jun;Cheng, Lan;Li, Xue-Tao
摘要肿瘤侵袭被认为是肿瘤转移的主要启动子，而肿瘤转移是导致大多数癌症相关死亡的原因。在本研究中，奥曲肽（OCT）修饰柔红霉素加双氢青蒿素脂质体的开发和表征。对乳腺癌MDA-MB-435 S细胞和MDA-MB-435 S异种移植物裸鼠进行评估。脂质体的大小为约100 nm，具有窄的多分散性指数。体外实验结果表明，OCT修饰的柔红霉素-双氢青蒿素脂质体可增强OCT-SSTRs（生长抑素受体）介导的主动靶向作用的细胞毒性和细胞摄取，并可通过掺入双氢青蒿素阻断肿瘤细胞的创伤愈合和迁移。其作用机制可能与调节乳腺癌细胞E-cadherin、α5β1-integrin、TGF-β1、VEGF和MMP 2/9有关。在体内，脂质体在MDA-MB-435 S异种移植小鼠中显示出延长的循环时间、更多的肿瘤部位蓄积和稳健的总体抗肿瘤功效，并且在测试剂量下没有明显的毒性。结论：OCT修饰柔红霉素联合双氢青蒿素脂质体能有效抑制乳腺癌的侵袭，为转移性乳腺癌的治疗提供了一种可能的策略。
Abstract Tumor invasion is considered a major promoter in the initiation of tumor metastasis, which is supposed to cause most cancer-related deaths. In the present study, octreotide (OCT)-modified daunorubicin plus dihydroartemisinin liposomes were developed and characterized. Evaluations were undertaken on breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts nude mice. The liposomes were ∼100 nm in size with a narrow polydispersity index. In vitro results showed that the OCT-modified daunorubicin plus dihydroartemisinin liposomes could enhance cytotoxicity and cellular uptake by OCT-SSTRs (somatostatin receptors)-mediated active targeting, block on tumor cell wound healing and migration by incorporating dihydroartemisinin. The action mechanism might be related to regulations on E-cadherin, α5β1-integrin, TGF-β1, VEGF and MMP2/9 in breast cancer cells. In vivo, the liposomes displayed a prolonged circulating time, more accumulation in tumor location, and a robust overall antitumor efficacy with no obvious toxicity at the test dose in MDA-MB-435S xenograft mice. In conclusion, the OCT-modified daunorubicin plus dihydroartemisinin liposomes could prevent breast cancer invasion, hence providing a possible strategy for treatment of metastatic breast cancer.