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A Combination Therapy of pHRE-Egr1-HSV-TK/Anti-CD133McAb-131I/MFH Mediated by FePt Nanoparticles for Liver Cancer Stem Cells
Journal of Nanomaterials Pub Date : 2020-06-12 , DOI: 10.1155/2020/7180613
Mei Lin 1 , Yanhong Xiao 2 , Xingmao Jiang 3 , Jun Zhang 4 , Ting Guo 5 , Yujuan Shi 2
Affiliation  

It has been evidenced that liver cancer stem cells (LCSCs) are to blame hepatocellular carcinoma (HCC) occurrence, development, metastasis, and recurrence. Using iron-platinum nanoparticles (FePt-NPs) as a carrier and CD133 antigen as a target, a new strategy to targetly kill LCSCs by integrating HSV-TK suicide gene, 131I nuclide irradiation, and magnetic fluid hyperthermia (MFH) together was designed and investigated in the present study. The results showed that FePt-NPs modified with PEI (PEI-FePt-NPs) could bind with DNA, and the best binding ratio was 1 : 40 (mass ratio). Moreover, DNA binding to PEI-FePt-NPs could refrain from Dnase1 enzyme digestion and could release under certain conditions. LCSCs (CD133+ Huh-7 cells) were transfected with pHRE-Egr1-HSV-TK by PEI-FePt-NPs, and the transfection efficiency was %. These data showed a good potential of PEI-FePt-NPs as a gene transfer carrier.131I was labeled with anti-CD133McAb in order to facilitate therapy targeting. The combined intervention of pHRE-Egr1-HSV-TK/anti-CD133McAb-131I/MFH mediated by PEI-FePt-NPs could greatly inhibit LCSCs’ growth and induce cell apoptosis in vitro, significantly higher than any of the individual interventions (). This study offers a practicable idea for LCSC treatment, and PEI-FePt-NPs may act as novel nonviral gene vectors and a magnetic induction medium.

中文翻译:

FePt纳米粒子介导的pHRE-Egr1-HSV-TK / Anti-CD133McAb-131I / MFH联合治疗肝癌干细胞

已有证据表明,肝癌干细胞(LCSC)归咎于肝细胞癌(HCC)的发生,发展,转移和复发。以铁铂纳米颗粒(FePt-NPs)为载体,以CD133抗原为靶标,设计了一种新的策略,通过整合HSV-TK自杀基因,131 I核素辐射和磁流体热疗(MFH)来杀死LCSC。并在本研究中进行了调查。结果表明,PEI修饰的FePt-NP(PEI-FePt-NPs)可以与DNA结合,最佳结合比例为1:40(质量比)。而且,与PEI-FePt-NPs结合的DNA可以抑制Dnase1酶的消化,并在一定条件下可以释放。LCSC(CD133 + 通过PEI-FePt-NPs用pHRE-Egr1-HSV-TK转染Huh-7细胞,转染效率为 %。这些数据表明,PEI-FePt-NPs作为基因转移载体的潜力很大。131 I用抗CD133McAb标记,以促进靶向治疗。PEI-FePt-NPs介导的pHRE-Egr1-HSV-TK / anti-CD133McAb- 131 I / MFH的联合干预可在体外显着抑制LCSCs的生长并诱导细胞凋亡,明显高于任何单独的干预措施()。这项研究为LCSC治疗提供了一个可行的想法,而PEI-FePt-NPs可以作为新型非病毒基因载体和磁感应介质。
更新日期:2020-06-12
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