The Synthesis Of Folate Targeted And Polymers Decorated Magnetic Nano Delivery Systems And Their Inhibition And Imaging Effects On Nasopharynx Cancer

Nasopharyngeal carcinoma(NPC)is a common metastatic malignancy in south China.Radiotherapy is the standard treatment of various stages of nasopharyngeal carcinoma,but there are a lot of complications after radiotherapy.The overall survival rate can be increased of nasopharyngeal carcinoma through chemotherapy,but the chemotherapy drugs are usually low targeted,and have a series of side effects.Gene therapy is another effective strategy for cancer therapy,but how to deliver genes to target cells effectively is also a big challenge.The use of nanotechnology to load the drugs and genes inside the nanoparticles,and deliver them into the tumor cells and then release the genes and drugs in cells could solve this problem effectively.Our previous studies showed that folate receptor was highly expressed in nasopharyngeal carcinoma cells,and we also synthesised folate decorated magnetic nanoparticles loading CDDP based of that.That magnetic nano composite could target and kill the nasopharyngeal carcinoma cells.However,the uptake efficiency of that magnetic nanoparticle is low.On the basis of our previous jobs,we prepared two kinds of folic acid-targeting magnetic nano-carriers to solved the previous problems.The cationic polymer mPEG-PLL-FA was prepared and was used to encapsulate the negatively charged cisplatin-loaded magnetic nanoparticles ASA-CDDP-MNP and the plasmid containing the tumor suppressor gene TFPI2 through electrostatic interaction to synthesize the nano composite mPEG-PLL-FA-TFPI2-ASA-MNPs-CDDP.The structure and physicochemical properties of magnetic nano-co-delivery system were detected by nuclear magnetic resonance spectroscopy,dynamic light scattering,low temperature transmission electron microscopy and magnetometer.Blood cell agglutination test,MTT assay and agarose gel electrophoresis were used to detect the biocompatibility and DNA protection.Prussian blue staining,fluorescence microscopy,Western blot were used to detect the targeting and gene transfection ability of magnetic nanoparticles.MTT,scratches,flow cytometry and plate clone formation were used for the detection of the prohibition ability of magnetic nano-co-delivery system,respectively.MRI T2 weighted imaging was used to detect the imaging effect of magnetic nano-co-delivery system in cells.The results showed that the magnetic nano-co-delivery system had good biocompatibility and excellent targeting ability,and had a strong inhibitory effect on nasopharyngeal carcinoma cell line HNE-1.But the system has the problem of low transfection efficiency.In order to overcome this problem,we used the folate-modified quaternary ammonium cationized hydroxyethyl cellulose to encapsulate the magnetic nanoparticles and adsorb the plasmid DNA to form the composite catHEC-FA @SPIO/pDNA.The products were characterized by nuclear magnetic resonance spectroscopy,infrared spectroscopy,UV spectroscopy,thermogravimetric analysis,X-ray diffraction,magnetization curves and transmission electron microscopy.MTT assay and agarose gel electrophoresis were used to detect the biocompatibility and DNA protection.Prussian blue staining,fluorescence microscopy,Western blot were used to detect the targeting and gene transfection ability of magnetic nanoparticles.MTT,and flow cytometry were used for the detection of the prohibition ability of magnetic nano-co-delivery system,respectively.MRI T2 weighted imaging was used to detect the imaging effect of magnetic nano-co-delivery system in cells.The results showed that catHEC-FA @ SPIO/pDNA had good biocompatibility,excellent targeting ability and high gene transfection efficiency,strong inhibitory effect on imaging of nasopharyngeal carcinoma cell line HNE-1.Folic acid-decorated quaternary ammonium cationic hydroxyethyl cellulose encapsulated magnetic nanoparticle composite catHEC-FA @ SPIO can be the vector of gene transfer and magnetic resonance imaging.