Nanoparticle-mediated radionuclide-gene therapy of liver cancer

摘要

The technique of nanoparticle-mediated radionuclide-gene therapy has been developed to promote targeted gene therapy of liver cancer. The AFP gene antisense oligonucleotide labeled with radioactive iodine-125 (125)~I-AFPasON was encapsulated with chitosan nanoparticle. Then the nanoparticles were transfected into the Hepatic cell cancer (HepG2 cell) to interfere its AFP gene expression. The transfection efficiency of the Nanoparticle-mediated radionuclide-gene, the target site of the gene, the AFP gene expression in the cell and its DNA damage were investigated using the techniques of nanoscale measurements such as confocal Raman scattering microscopy and multi-dimensional microscopy. All the parameters were measured as functions of the radiation intensity, the time of the transfection, and the size of the nanoparticle. It was found that Auger electron emitted from iodine-125 could damage the helical conformation and structure of DNA, and depress the AFP gene expression. The DNA damage increased with the radiation intensity. The asON is an effective specific carrier of the radionuclide iodine-125 into the target DNA. Mediated by chitosan nanoparticles, the effect of the (I25)~I-AFPasON on the DNA damage of the HepG2 cell can be enhanced to over twice.