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首页> 外文期刊>RSC Advances >Delivery of siRNA targeting HIF-1α loaded chitosan modified d-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) nanoparticles into nasopharyngeal carcinoma cell to improve the therapeutic efficacy of cisplatin
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Delivery of siRNA targeting HIF-1α loaded chitosan modified d-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) nanoparticles into nasopharyngeal carcinoma cell to improve the therapeutic efficacy of cisplatin

机译：递送siRNA靶向HIF-1α装载的壳聚糖改性的D-α-生育酰基聚乙二醇1000琥珀酸酯-B-聚（ε-己内酯 - 甘油）纳米粒子进入鼻咽癌细胞，以提高顺铂的治疗效果

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Hypoxia inducible factor-1α (HIF-1α) related signaling pathways mediating chemoresistance has been found in various kinds of cancer, including nasopharyngeal carcinoma (NPC). In this research, a chitosan modified D -α-tocopheryl polyethylene glycol 1000 succinate- b -poly(ε-caprolactone- ran -glycolide) (TPGS- b -(PCL- ran -PGA)) nanoparticle (NP) was prepared for small interfering ribonucleic acid (siRNA) targeting HIF-1α delivery. The results showed that chitosan-modified TPGS- b -(PCL- ran -PGA) NPs could effectively deliver siRNA into CNE-2 cells, resulting in the decrease of HIF-1α expression and cell viability. Decreased sensitivity of cisplatin in CNE-2 cells under hypoxia condition was correlated with the overexpression of HIF-1α and multiple drug resistance gene 1 (MDR1)/P-glycoprotein (P-gp). Inhibiting HIF-1α by siRNA targeting HIF-1α loaded chitosan modified TPGS- b -(PCL- ran -PGA) NPs significantly decreased the expression of HIF-1α and MDR1/P-gp and restored the effect of cisplatin on CNE-2 cells. Moreover, synergistic anti-tumor effects could be achieved by the combined use of siRNA targeting HIF-1α loaded chitosan modified TPGS- b -(PCL- ran -PGA) NPs and cisplatin. These findings showed that the chitosan modified TPGS- b -(PCL- ran -PGA) NPs could function as an effective carrier for siRNA delivery aiming at modulating HIF-1α expression to increase the therapeutic potential of cisplatin in NPC therapy.
机译：在各种癌症中发现介导化学抑制的缺氧诱导因子-1α（HIF-1α）相关信号通路，包括鼻咽癌（NPC）。在本研究中，制备壳聚糖改性的D-α-生育酰基聚乙二醇1000琥珀酸酯-B - 聚（ε-己内酯 - 乙酰乙醛）（TPGS-B - （PCL- RAN-（PCL- RAN-（PCL- RAN-（PCL- RAN-））纳米颗粒（NP）干扰核糖核酸（siRNA）靶向HIF-1α递送。结果表明，壳聚糖改性的TPGS-B - （PCL- RAN -PGA）NPS可以有效地将siRNA递送到CNE-2细胞中，导致HIF-1α表达和细胞活力降低。在缺氧条件下降低CNE-2细胞中的顺铂的敏感性与HIF-1α和多种药物抗性基因1（MDR1）/ p-糖蛋白（P-GP）的过表达相关。通过siRNA靶向HIF-1α的HIF-1α加载的壳聚糖改性TPGS-B - （PCL-RAN -PGA）NPS显着降低了HIF-1α和MDR1 / P-GP的表达，并恢复了顺铂对CNE-2细胞的影响。此外，通过组合使用SiRNA靶向HIF-1α负载的壳聚糖修饰的TPGS-B - （PCL- RAN -PGA）NPS和顺铂，可以实现协同抗肿瘤效应。这些发现表明，壳聚糖改性的TPGS-B - （PCL- RAN -PGA）NPS可以用作旨在调节HIF-1α表达的siRNA递送的有效载体，以增加顺铂治疗NPC疗法的治疗潜力。

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