A Combination Therapy of pHRE-Egr1-HSV-TK/Anti-CD133McAb-¹³¹I/MFH Mediated by FePt Nanoparticles for Liver Cancer Stem Cells

Abstract

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 53.65±3.40%. 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 (p<0.05). 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.

The therapeutic effect and MR molecular imaging of FA-PEG-FePt/DDP nanoliposomes in AMF on ovarian cancer

“… 19 , 41 The results of our previous study suggested FePt-NPs had a property to generate heat in AMF. 42 In the present work, we prepared FA-FePt/DDP-NPs and integrated folate receptor-targeting DDP and MFH to intervene ovarian cancer. As a result, ovarian cancer cells were significantly inhibited in proliferation, migration, and invasion and induced to apoptosis in vitro.…”

“…Oleic acid-coated ferro platinum magnetic nanoparticles (FePt-NPs) were prepared by a high-temperature liquid-phase reduction method according to the reference. 29 In detail, 60 mg DSPE-PEG 2000 powder was dissolved in 5 mL trichloromethane, and 3 mL FePt-NPs (the concentration was 5 mg Fe/mL and dispersed in chloroform) were removed. Then the two were mixed into a round-bottom flask.…”

The role of oncolytic virotherapy and viral oncogenes in the cancer stem cells: a review of virus in cancer stem cells

“…Another study discovered a novel method to target kill LCSCs by combining the HSV-TK suicide gene, nuclide 131I irradiation, and magnetic fluid hyperthermia (MFH) with iron-platinum nanoparticles (FePt-NPs) as a carrier and CD133 antigen as a target. In comparison to any of the individual treatments, the combination intervention of pHRE-Egr1-HSV-TK/anti-CD133McAb-131I/MFH mediated by PEI-FePt-NPs may dramatically reduce LCSCs’ growth and trigger cell death in vitro [ 86 ].…”