Application of superparamagnetic iron oxide labeled antisense oligodeoxynucleotide probe in cellular magnetic resonance imaging / 中国医学科学院学报

<p><b>OBJECTIVE</b>To prepare the superparamagnetic iron oxide (SPIO)-labeled antisense oligodeoxynucleotide (ASODN) probe and evaluate the application of this probe in cellular magnetic resonance imaging (MRI).</p><p><b>METHODS</b>We prepared the SPIO-labeled ASODN probe using chemical cross linking method to conjugate SPIO to ASODN, detected its configuration by atomic force microscopy, determined the conjugating rate and biology activation by high performance liquid chromatography, and detected the stability by polyacrylamide gel electrophoresis. After that, we transfected the SK-Br3 oncocytes which had over-expression of the c-erbB2 oncogene by this probes, observed the intracellular iron distribution by optical microscope, measured iron content by atomic absorption spectroscopy, and observed the signal change by MRI.</p><p><b>RESULTS</b>Atomic force microscope showed that the SPIO-labeled ASODN probe was mostly spherical and well-distributed, with a diameter of 25-40 nm and a conjugating rate of 100%. This probe had inhered biological activity and stability. In addition, light microscopy revealed an intracellular uptake of iron oxides in the transfected SK-Br3 oncocyte, and the iron content of the group of transfected SK-Br3 oncocytes was significantly higher than those of other contrast groups (all P < 0.01). MRI showed that transfected SK-Br3 oncocyte had the lowest signal among all other cells (all P < 0.05).</p><p><b>CONCLUSIONS</b>We prepared the SPIO-labeled ASODN probe successfully. It can effectively transfect SK-Br3 oncocyte and enter SK-Br3 oncocyte, and thus reduce the signal intension in MRI.</p>

Reversion of multidrug resistance of hepatocellular carcinoma by antisense oligonucleotides and ultrasonic microbubble intensifier transfection combined with ultrasound irradiation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study whether antisense oligonucleotides and ultrasonic microbubble intensifier transfection combined with ultrasound irradiation is an effective and directional way in reversing multidrug resistance (MDR) in tumors.</p><p><b>METHODS</b>Mdr1, mrp, and lrp genes antisense oligonucleotides on the ultrasound microbubble intensifier were transfected for the human HepG2/ADM cell lines and then the cells were radiated with low intensity ultrasound. The effects of the reversion of carcinoma cells' MDR and the reduction of their malignancy and growth capability in vitro and in vivo were assessed using RT-PCR, Western blot and MTT.</p><p><b>RESULTS</b>The treatment restrained the multiplication of the human HepG2/AMD cell lines. The levels of their mRNA and protein of cells' mdr1 and mrp genes dropped significantly. Growth of the subcutaneous transplanted tumors in the nude mice decreased.</p><p><b>CONCLUSIONS</b>Transfection of MDR genes antisense oligonucleotides on the ultrasonic microbubble intensifier combined with low intensity ultrasound radiation may serve as a new treatment method for hepatocellular carcinoma.</p>