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

机译：将靶向HIF-1α的壳聚糖修饰的D-α-生育酚聚乙二醇1000琥珀酸酯-b-聚（ε-己内酯-ran-乙交酯）纳米颗粒递送到鼻咽癌细胞中以提高顺铂的疗效

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摘要

Hypoxia inducible factor-1 alpha (HIF-1 alpha) related signaling pathways mediating chemoresistance has been found in various kinds of cancer, including nasopharyngeal carcinoma (NPC). In this research, a chitosan modified D-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was prepared for small interfering ribonucleic acid (siRNA) targeting HIF-1 alpha 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-1 alpha expression and cell viability. Decreased sensitivity of cisplatin in CNE-2 cells under hypoxia condition was correlated with the overexpression of HIF-1 alpha and multiple drug resistance gene 1 (MDR1)/P-glycoprotein (P-gp). Inhibiting HIF-1 alpha by siRNA targeting HIF-1 alpha loaded chitosan modified TPGS-b-(PCL-ran-PGA) NPs significantly decreased the expression of HIF-1 alpha 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-1 alpha 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-1 alpha expression to increase the therapeutic potential of cisplatin in NPC therapy.
机译：缺氧诱导因子-1α（HIF-1 alpha）相关的介导化学抗性的信号传导途径已在包括鼻咽癌（NPC）在内的各种癌症中被发现。在这项研究中，制备了壳聚糖修饰的D-α-生育酚聚乙二醇1000琥珀酸酯-b-聚（ε-己内酯-丙交酯）（TPGS-b-（PCL-ran-PGA））纳米颗粒（NP）靶向HIF-1α传递的干扰核糖核酸（siRNA）。结果表明，壳聚糖修饰的TPGS-b-（PCL-ran-PGA）NPs可以有效地将siRNA传递到CNE-2细胞中，导致HIF-1 alpha表达和细胞活力降低。缺氧条件下，CNE-2细胞中顺铂敏感性降低与HIF-1α和多重耐药基因1（MDR1）/ P-糖蛋白（P-gp）的过度表达有关。靶向HIF-1 alpha的壳聚糖修饰的TPGS-b-（PCL-ran-PGA）NPs的siRNA抑制HIF-1 alpha显着降低了HIF-1 alpha和MDR1 / P-gp的表达并恢复了顺铂对CNE的作用-2个单元格。此外，可以通过联合使用靶向HIF-1α的壳聚糖修饰的TPGS-b-（PCL-ran-PGA）NP和顺铂的siRNA达到协同抗肿瘤作用。这些发现表明，壳聚糖修饰的TPGS-b-（PCL-ran-PGA）NPs可以作为siRNA传递的有效载体，目的在于调节HIF-1α表达以增加顺铂在NPC治疗中的治疗潜力。

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