Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles

Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles
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DOI:
10.1016/j.biomaterials.2013.12.095
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发表时间:
2014-03-01
期刊:
影响因子:
14
通讯作者:
Xu, Zhi P.
Xu, Zhi P.
中科院分区:
工程技术1区
文献类型:
--
作者:
Li, Li;Gu, Wenyi;Xu, Zhi P.

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在这项研究中,我们采用层状双氢氧化物纳米颗粒(LDHs)同时递送抗癌药物5-氟尿嘧啶(5-FU)和Allstars细胞死亡siRNA(CD-siRNA),以有效治疗癌症。该策略利用LDH的阴离子交换能力将5-FU插入其层间距并将siRNA负载在LDH纳米颗粒表面。LDH纳米颗粒先前已在各种研究中分别被证明是5-FU和siRNA的有效细胞递送系统。更令人兴奋的是,与使用CD-siRNA或5-FU的单一治疗相比,CD-siRNA和抗癌药物5-FU与相同LDH颗粒的组合显著增强了对三种癌细胞系(例如MCF-7、U2 OS和HCT-116)的细胞毒性。这种增强可能是线粒体协同损伤过程的结果。因此,通过LDHs共递送siRNA和抗癌药物的策略具有克服耐药性和增强癌症治疗的巨大潜力。(C)2014爱思唯尔有限公司版权所有。
In this research we employed layered double hydroxide nanoparticles (LDHs) to simultaneously deliver an anticancer drug 5-fluorouracil (5-FU) and Allstars Cell Death siRNA (CD-siRNA) for effective cancer treatment. The strategy takes advantage of the LDH anion exchange capacity to intercalate 5-FU into its interlayer spacing and load siRNA on the surface of LDH nanoparticles. LDH nanoparticles have been previously demonstrated as an effective cellular delivery system for 5-FU and siRNA separately in various investigations. More excitedly, the combination of CD-siRNA and anticancer drug 5-FU with the same LDH particles significantly enhanced cytotoxicity to three cancer cell lines, e.g. MCF-7, U2OS and HCT-116, compared to the single treatment with either CD-siRNA or 5-FU. This enhancement is probably a result of coordinate mitochondrial damage process. Thus, the strategy to co-deliver siRNA and an anticancer drug by LDHs has great potential to overcome the drug resistance and enhance cancer treatment. (C) 2014 Elsevier Ltd. All rights reserved.