Journal of Drug Targeting ( IF 4.5 ) Pub Date : 2020-06-16 , DOI: 10.1080/1061186x.2020.1775839 Jie Zhao 1 , Bin Wen 2 , Zhengbing Tan 3 , Xinyan Li 4 , Xuesong Zhang 5
Abstract
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 Ca2+ 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 Ca2+ channel siRNA was proved to reverse the MDR within the cells of cancer by regulation the T-type Ca2+ channels. Our results showed that decreased expression of T-type Ca2+ channels resulted in lowered cytosolic Ca2+ level responsible for the cell cycle arrest (at G0/G1 phase) as well as elevated cellular drug retention in HepG2/Adr. B in vitro/in vivo experiments revealed that LSC/R-A exerted highly elevated therapeutic outcome on HepG2/Adr, than administration of single siRNA or Adr.
中文翻译:
iRGD 靶向混合纳米粒子逆转多重耐药性,有效对抗肝癌。
摘要
脱靶给药以及多药耐药性(MDR)被普遍认为是导致化疗在癌症临床治疗中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 修饰的脂质包覆二氧化硅 (LSC) 纳米颗粒,共同递送 Ca 2+通道 siRNA 和阿霉素 (Adr) 以逆转肝癌 (LSC/RA) 中的 MDR。建议 iRGD 装饰提高药物递送系统 (DDS) 的肿瘤积累。此外,Ca 2+通道siRNA的引入被证明可以通过调节T型Ca 2+通道来逆转癌细胞内的MDR 。我们的结果表明,T 型 Ca 2+ 的表达降低通道导致导致细胞周期停滞(G0/G1 期)的细胞溶质 Ca 2+水平降低以及 HepG2/Adr 中细胞药物保留升高。B体外/体内实验表明,LSC/RA 对 HepG2/Adr 的治疗效果比施用单个 siRNA 或 Adr 高。