...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>ACS applied materials & interfaces >Gemcitabine and Antisense-microRNA Co-encapsulated PLGA-PEG Polymer Nanoparticles for Hepatocellular Carcinoma Therapy
【24h】

Gemcitabine and Antisense-microRNA Co-encapsulated PLGA-PEG Polymer Nanoparticles for Hepatocellular Carcinoma Therapy

机译：吉西他滨和反义-microRNA共包裹的PLGA-PEG聚合物纳米颗粒用于肝细胞癌的治疗

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Hepatocellular carcinoma (HCC) is highly prevalent, and the third most common cause of cancer associated deaths worldwide. HCC tumors respond poorly to chemotherapeutic anticancer agents due to inherent and acquired drug resistance, and low drug permeability. Targeted drug delivery systems with significant improvement in therapeutic efficiency are needed for successful HCC therapy. Here, we report the results of a technique optimized for the synthesis and formulation of antisense-miRNA-21 and gemcitabine (GEM) co-encapsulated PEGylated-PLGA nano particles (NPs) and their in vitro therapeutic efficacy in human HCC (Hep3B and HepG2) cells. Water-in-oil-in-water (w/o/w) double emulsion method was used to coload antisense-miRNA-21 and GEM in PEGylated-PLGA-NPs. The cellular uptake of NPs displayed time dependent increase of NPs concentration inside the cells. Cell viability analyses in HCC (Hep3B and HepG2) cells treated with antisense-miRNA-21 and GEM co-encapsulated NPs demonstrated a nanoparticle concentration dependent decrease in cell proliferation, and the maximum therapeutic efficiency was attained in cells treated with nanoparticles co-encapsulated with antisense-miRNA-21 and GEM. Flow cytometry analysis showed that control NPs and antisense-miRNA-21-loaded NPs are not cytotoxic to both HCC cell lines, whereas treatment with free GEM and GEM-loaded NPs resulted in similar to 9% and similar to 15% apoptosis, respectively. Cell cycle status analysis of both cell lines treated with free GEM or NPs loaded with GEM or antisense-miRNA-21 displayed a significant cell cycle arrest at the S-phase. Cellular pathway analysis indicated that Bcl2 expression was significantly upregulated in GEM treated cells, and as expected, PTEN expression was noticeably upregulated in cells treated with antisense-miRNA-21. In summary, we successfully synthesized PEGylated-PLGA nanoparticles co- encapsulated with antisense-miRNA-21 and GEM. These co-encapsulated nanoparticles revealed increased treatment efficacy in HCC cells, compared to cells treated with either antisense-miRNA-21- or GEM-loaded NPs at equal concentration, indicating that down-regulation of endogenous miRNA-21 function can reduce HCC cell viability and proliferation in response to GEM treatment.
机译：肝细胞癌（HCC）高度流行，是全世界与癌症相关的死亡的第三大最常见原因。由于固有的和获得性的耐药性以及低的药物渗透性，HCC肿瘤对化疗抗癌药的反应较差。成功的HCC治疗需要具有治疗效率显着改善的靶向药物递送系统。在这里，我们报告了针对反义miRNA-21和吉西他滨（GEM）共封装的聚乙二醇化PLGA纳米颗粒（NPs）的合成和配方优化技术的结果，以及它们在人肝癌中的体外治疗功效（Hep3B和HepG2 ） 细胞。使用水包油包水（w / o / w）双乳化法将反义miRNA-21和GEM共同负载在聚乙二醇化的PLGA-NP中。 NPs的细胞摄取显示出细胞内NPs浓度随时间的增加。用反义miRNA-21和GEM共包裹的NP处理的HCC细胞（Hep3B和HepG2）中的细胞活力分析表明，纳米粒浓度依赖于细胞增殖的降低，并且在用纳米粒共包裹的纳米颗粒处理的细胞中获得了最大的治疗效率反义miRNA-21和GEM。流式细胞仪分析表明，对照NPs和反义miRNA-21加载的NPs对两种HCC细胞系均无细胞毒性，而用游离GEM和GEM加载的NPs处理则分别导致接近9％和接近15％的细胞凋亡。用游离GEM或载有GEM或反义miRNA-21的NP处理的两种细胞系的细胞周期状态分析显示，在S期有明显的细胞周期停滞。细胞途径分析表明，在创业板处理过的细胞中Bcl2表达明显上调，并且正如预期的那样，在用反义miRNA-21处理过的细胞中PTEN表达明显上调。总之，我们成功地合成了与反义miRNA-21和GEM共包裹的PEG化PLGA纳米颗粒。与以相同浓度的反义-miRNA-21或GEM加载的NPs处理的细胞相比，这些共包封的纳米颗粒显示出在HCC细胞中增强的治疗功效，表明内源性miRNA-21功能的下调可降低HCC细胞的生存能力和对GEM处理的增殖。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号