Using thermal energy produced by irradiation of Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression.
One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we developed a novel heat-inducible gene expression system in which thermal energy generated by Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) under an alternating magnetic field (AMF) was used to activate gene expression. MZF-NPs, obtained by co-precipitation method, were firstly surface modified with cation poly(ethylenimine) (PEI). Then thermodynamic test of various doses of MZF-NPs was preformed in vivo and in vitro. PEI-MZF-NPs showed good DNA binding ability and high transfection efficiency. In AMF, they could rise to a steady temperature. To analyze the heat-induced gene expression under an AMF, we combined P1730OR vector transfection with hyperthermia produced by irradiation of MZF-NPs. By using LacZ gene as a reporter gene and Hsp70 as a promoter, it was demonstrated that expression of a heterogeneous gene could be elevated to 10 to 500-fold over background by moderate hyperthermia (added 12.24 or 25.81 mg MZF-NPs to growth medium) in tissue cultured cells. When injected with 2.6 or 4.6 mg MZF-NPs, the temperature of tumor-bearing nude mice could rise to 39.5 or 42.8 degrees C, respectively, and the beta-gal concentration could increase up to 3.8 or 8.1 mU/mg proteins accordingly 1 day after hyperthermia treatment. Our results therefore supported hyperthermia produced by irradiation of MZF-NPs under an AMF as a feasible approach for targeted heat-induced gene expression. This novel system made use of the relative low Curie point of MZF-NPs to control the in vivo hyperthermia temperature and therefore acquired safe and effective heat-inducible transgene expression.
Tang
Qiu-sha
QS
School of Clinical Medical Science, Southeast University, Nanjing 210009, China.
Zhang
Dong-sheng
DS
Cong
Xiao-ming
XM
Wan
Mei-ling
ML
Jin
Li-qiang
LQ
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000532:radiotherapy; D002460:Cell Line; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005290:Ferric Compounds / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D006979:Hyperthermia, Induced; D007668:Kidney / Q000166:cytology; D007763:Lac Operon; D008113:Liver Neoplasms / Q000473:pathology / Q000532:radiotherapy; D008156:Luciferases / Q000378:metabolism; D008280:Magnetics / Q000627:therapeutic use; D008297:Male; D017895:Manganese Compounds / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000528:radiation effects*; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011897:Random Allocation; D013816:Thermodynamics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D017967:Zinc Compounds / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects*; D001616:beta-Galactosidase / Q000032:analysis / Q000378:metabolism
D020099:Coated Materials, Biocompatible; D005290:Ferric Compounds; D018840:HSP70 Heat-Shock Proteins; D017895:Manganese Compounds; D017967:Zinc Compounds; C039048:manganese-zinc ferrite; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases; D001616:beta-Galactosidase