Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.
Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.
复制标题
脂质包被的顺铂纳米粒负载 MicroRNA-375 的抗肿瘤效果
DOI：
10.7150/thno.13130
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发表时间：
2016
期刊：
影响因子：
12.4
通讯作者：
Xiang G
中科院分区：
文献类型：
--
作者：
Yang T;Zhao P;Rong Z;Li B;Xue H;You J;He C;Li W;He X;Lee RJ;Ma X;Xiang G
肝细胞癌（HCC）治疗的主要挑战之一是其对化疗药物不敏感。在此，我们报告了共同负载 microRNA-375 (NPC/miR-375) 的新型脂质涂层顺铂纳米颗粒的开发，作为化疗不敏感 HCC 的潜在治疗方法。 NPC/miR-375 是通过混合两种含有 KCl 溶液和涂有阳离子脂质层的高溶解度顺式二胺二氢铂 (II) 的反相微乳液来制备的。随后，将 miR-375 掺入脂质包被的顺铂纳米颗粒中。 NPC/miR375纳米粒子有望进一步降低细胞增殖并增强顺铂在化疗耐药性肝癌细胞中的抗肿瘤作用。细胞内运输的体外分析表明，NPC/miR-375 能够从晚期内涵体而不是溶酶体中逃逸，从而避免了 miR-375 在溶酶体中的降解。重要的是，NPC/miR-375 在体外增强了 HCC 细胞的凋亡并诱导细胞周期停滞。在双癌基因 Akt/Ras 诱导的原发性 HCC 小鼠模型中，多次剂量的 NPC/miR-375 显着抑制肿瘤生长并延缓肿瘤复发。我们的结果表明，与 miR-375 共负载的顺铂纳米颗粒是化疗不敏感 HCC 的潜在治疗剂。
One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 was fabricated by mixing two reverse microemulsions containing KCl solution and a highly soluble cis-diaminedihydroplatinum (II) coated with a cationic lipid layer. Subsequently, the miR-375 was incorporated into the lipid-coated cisplatin nanoparticles. The NPC/miR375 nanoparticles were expected to further decrease cell proliferation and to enhance the anti-tumor effect of cisplatin in chemotherapy resistant HCC cells. In vitro analysis of intracellular trafficking revealed that NPC/miR-375 were able to escape from the late endosomes instead of lysosomes thus avoiding degradation of the miR-375 in lysosomes. Importantly, NPC/miR-375 enhanced apoptosis and induced cell cycle arrest in HCC cells in vitro. In the double oncogenes Akt/Ras-induced primary HCC mouse model, multiple doses of NPC/miR-375 significantly inhibited tumor growth and delayed the tumor relapse. Our results indicate that cisplatin nanoparticles co-loaded with miR-375 represent a potential therapeutic agent for chemotherapy-insensitive HCC.