Synthesis And Application Of Paramagnetic Nanoparticles For The Targeted Carrier Of Anticancer Drugs

Magnetocaloric effect will be generated when paramagnetic nanoparticles （MNP）are located in alternating magnetic field, which has a promising future in treatingtumor with hyperthermia. At present, MNP has made some progress in implantingtumor topically to investigate local hyperthermia research. However, there are stillsome limitations on the MNP’s application in the systemic treatment, especially inmalignant cancer treatment. Therefore, it is extremely siginificant to develop an activetargeting and long-circulating MNP as a carrier of anticancer drugs to tumor sites inthe systemic treatment.In this research, the folate （FA）-grafted MNP, Fe₃O₄-PLA-MPEG/PEG-FA withFe₃O₄as the core, the amphiphilic polymer of polylactic acid-co-methoxypolyethylene glycol （PLA-MPEG） or/and polylactic acid-co-folate-conjugatedpolyethylene glycol （PLA-PEG-FA） as the shell were designed. Due to thehydrophobic effect, PLA segment can load hydrophobic anticancer drugs. PEGsegment can improve water-dispersion of nanoparticles, and extend the circulationtime in vivo. FA was grafted on PEG partially as the active targeting agent of tumor.3-aminopropyltrimethoxysilane （APS） was used as the chemical bridge link betweenmagnetic cores and polymer shells to avoid polymers’ physical separation frommagnetic surface.The magnetic particles were characterized by X-ray diffraction （XRD）, X-rayphotoelectron spectroscopy （XPS）, vibrating sample magnetometer （VSM）,transmission electron microscopy （TEM）, et al. The core Fe₃O₄was determined asface-centered cubic crystal and paramagnetism. The mean size of nanoparticles isabout100nm, with a narrow size distribution, which makes it suitable for anticancerdrug delivery applications because of the EPR （Enhanced Permeation and Retention）effect.The ratio of FA grafted on PEG has greate impact on the stability of magneticnanoparticles in water. When the graft ratio of FA on PEG was about20%, thenanoparticles were well dispersed into water. Results of the hemolysis tests showedthat the magnetic nanoparticles had a good biocompatibility without cell agglutinationand hemolysis phenomenon. Paclitaxel as the model drug was embedded in hydrophobic segment ofnanoparticles through in post-embedding method. Since the core was occupied byFe₃O₄, only a small mount of drugs were entaraped into the nanoparticles throughhydrophobic interaction between PLA and paclitaxel. The drug release results showedthat the nanoparticles could provide the sustained release of drug.These results indicate that Fe₃O₄-PLA-MPEG/PEG-25%FA would be a suitablecarrier for hydrophobic anticancer drugs and has a good prospect of application in themalignant tumors treatment.