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首页> 外文期刊>Journal of drug targeting >iRGD-targeted hybrid nanoparticles reverses multi-drug resistant to effectively combat liver cancer
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iRGD-targeted hybrid nanoparticles reverses multi-drug resistant to effectively combat liver cancer

机译：IRGD靶向杂交纳米粒子逆转多种毒性，以有效地打击肝癌

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摘要

The off-target delivery as well as multi-drug resistance (MDR) are generally recognised as two keys difficulties responsible for the poor performance of chemotherapy in clinical treatment of cancer. With the aim to address the problems, we herein constructed iRGD modified and lipid-coated silica (LSC) nanoparticles co-delivering Ca(2+)channel siRNA and adriamycin (Adr) to reverse the MDR in liver cancer (LSC/R-A). The iRGD decoration was suggested to elevate the tumour accumulation of the drug delivery system (DDS). In addition, the introduction of Ca(2+)channel siRNA was proved to reverse the MDR within the cells of cancer by regulation the T-type Ca(2+)channels. Our results showed that decreased expression of T-type Ca(2+)channels resulted in lowered cytosolic Ca(2+)level responsible for the cell cycle arrest (at G0/G1 phase) as well as elevated cellular drug retention in HepG2/Adr. Bin vitro/in vivoexperiments revealed that LSC/R-A exerted highly elevated therapeutic outcome on HepG2/Adr, than administration of single siRNA or Adr.
机译：非靶向给药和多药耐药（MDR）通常被认为是导致癌症临床治疗中化疗表现不佳的两个关键困难。为了解决这些问题，我们在此构建了iRGD修饰的脂质包裹二氧化硅（LSC）纳米粒，共递送Ca（2+）通道siRNA和阿霉素（Adr），以逆转肝癌（LSC/R-A）中的多药耐药性。iRGD修饰可以提高药物释放系统（DDS）的肿瘤蓄积。此外，Ca（2+）通道siRNA的引入被证明可以通过调节T型Ca（2+）通道逆转癌细胞内的MDR。我们的研究结果表明，T型钙通道的表达降低导致细胞内钙离子水平降低，导致细胞周期停滞（G0/G1期）以及HepG2/Adr中细胞药物滞留增加。体外/体内实验表明，LSC/R-A对HepG2/Adr的治疗效果比单一siRNA或Adr的治疗效果高。

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