title: A combination hepatoma-targeted therapy based on nanotechnology: pHRE-Egr1-HSV-TK/(131)I-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/(131)I-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 (131)I 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/(131)I-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.
authors.affiliation: Taizhou People's Hospital Affiliated to Nantong University, Taizhou, 225300, China.|Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Lin
authors.affiliation: Taizhou People's Hospital Affiliated to Nantong University, Taizhou, 225300, China.
authors.forename: Junxing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Key Laboratory of Advanced Catalytic Material and Technology, Changzhou University, Changzhou, 213000, China.
authors.forename: Xingmao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Taizhou People's Hospital Affiliated to Nantong University, Taizhou, 225300, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Taizhou People's Hospital Affiliated to Nantong University, Taizhou, 225300, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.affiliation: Medical School of Southeast University, Nanjing, 210009, China.|Southeast University, Jiangsu Key Laboratory For Biomaterials and Devices, Nanjing, 210009, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology / Q000628:therapy* / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006801:Humans; D006979:Hyperthermia, Induced; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy* / Q000648:ultrastructure; D008280:Magnetics; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D036103:Nanotechnology; D009336:Necrosis; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry; D015183:Restriction Mapping; D018139:Simplexvirus / Q000378:metabolism*; D013696:Temperature; D013937:Thymidine Kinase / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D007457:Iodine Radioisotopes; D011094:Polyethyleneimine; D013937:Thymidine Kinase; D015774:Ganciclovir