A combination hepatoma-targeted therapy based on nanotechnology: pHRE-Egr1-HSV-TK/131I-antiAFPMcAb-GCV/MFH

Abstract

Combination targeted therapy is a promising cancer therapeutic strategy. Here, using PEI-Mn0.5Zn0.5Fe2O4 nanoparticles (PEI-MZF-NPs) as magnetic media for MFH (magnetic fluid hyperthermia) and gene transfer vector for gene-therapy, a combined therapy, pHRE-Egr1-HSV-TK/131I-antiAFPMcAb-GCV/MFH, for hepatoma is developed. AntiAFPMcAb (Monoclonal antibody AFP) is exploited for targeting. The plasmids pHRE-Egr1-HSV-TK are achieved by incorporation of pEgr1-HSV-TK and pHRE-Egr1-EGFP. Restriction enzyme digestion and PCR confirm the recombinant plasmids pHRE-Egr1-HSV-TK are successfully constructed. After exposure to the magnetic field, PEI-MZF-NPs/pHRE-Egr1-EGFP fluid is warmed rapidly and then the temperature is maintained at 43 °C or so, which is quite appropriate for cancer treatment. The gene expression reaches the peak when treated with 200 μCi 131I for 24 hours, indicating that the dose of 200 μCi might be the optimal dose for irradiation and 24 h irradiation later is the best time to initiate MFH. The in vitro and in vivo experiments demonstrate that pHRE-Egr1-HSV-TK/131I-antiAFPMcAb-GCV/MFH can greatly suppress hepatic tumor cell proliferation and induce cell apoptosis and necrosis and effectively inhibit the tumor growth, much better than any monotherapy does alone. Furthermore, the combination therapy has few or no adverse effects. It might be applicable as a strategy to treat hepatic cancer.

Biological Characteristics and Carrier Functions of Pegylated Manganese Zinc Ferrite Nanoparticles

“…When the mass ratio of magnetic NPs to CD44-shRNA was 40 : 1, the former could practically bind with all plasmids in the system (Figure 6(a)) indicating 40 : 1 was an optimal binding ratio. Within 1,4,8,12, and 24 h and 2 d, DNA was released at a large amount. But it was not greatly different between day 3 and day 4, and PEG-MZF-NPs could protect the plasmids and effectively release DNA (Figure 6(b)).…”

“…Owing to some special properties such as easy modifiability, good biocompatibility, little immune response, and being easily coupled with other ligands and easily organized with specific cell surface receptors or swallowed up by target cells and high efficiency rate gene transfer, nanoparticles can be made as ideal carriers [3]. Apart from the general functions of a nanocarrier, magnetic nanoparticles can produce a thermal effect in an alternating magnetic field and hence may be used for tumor hyperthermia [4,5].…”

“…Among them, manganese zinc ferrite (Mn 0.6 Zn 0.4 Fe 2 O 4 , Mn 0.5 Zn 0.5 Fe 2 O 4 ) nanoparticles have been used as vectors in suicide gene HSV-TK therapy for hepatoma and showed a satisfactory effect [6]. Moreover, manganese zinc ferrite nanoparticles also possess automatic temperature control and homoeothermic features [4,7]. It is considered that manganese zinc ferrite nanoparticles may be used as a vehicle for CD44-shRNA therapy and function as a magnetic medium for magnetic thermotherapy on ovarian cancer.…”

The Recent Advances of Magnetic Nanoparticles in Medicine

“…Using Mn0.5Zn0.5Fe2O4 as vector, Lin et al combined radionuclide, suicide gene, and MFH organically to treat liver cancer. The results indicated an excellent effect, and the tumor inhibition rate of the combined therapy group was remarkably higher than that of any other single therapy [71]. Another research showed that magnetic cAs 2 O 3 /Fe 2 O 3 nanocomposites adopted to thermochemotherapy for hepatoma had an evident higher effect than that of the single thermotherapy and the As 2 O 3 chemotherapy alone and the equivalent dosage of chemotherapeutics was greatly lowed and has few side effects [72].…”

131I radiolabeled immune albumin nanospheres loaded with doxorubicin for in vivo combinatorial therapy

“…131 I-antiAFPMcAb was prepared with chloramine-T method according to the previous report. 13 Briefly, 75-μL antiAFPMcAb and 5-μL Na 131 I (~4 mCi) were mixed in pH 7.2 PBS solution, and then chloramine-T was added to the mixture. After 1 minute, the crude product was purified on a PD10 column.…”