The Synthesis and Characterizations of O-Carboxymethyl-Chitosan Ultra-small Superparamagnetic Iron Oxide Nanoparticles

OBJECTIVE To develop a novel USPIO-NPs system by surface-modifying superparamagnetic iron oxide nanoparticles(USPIO-NPs) with O-carboxymethyl-chitosans(OCMCS) to improve their biocompatibility and ability to evade reticuloendothelial system(RES).METHODS The OCMCS-USPIO-NP was synthesized by two-step methods: at first,the plain SPIO-NPs was synthesize by alkaline co-precipitation,then the surface of the SPIO-NPs were modified by conjugating the OCMCS to USPIO-NPs,orthogonal experimental design of L9(34) was used to optimize the technology of preparing OCMCS-USPIO-NPs.The resulting USPIO nanoparticles were characterized by dynamic light scattering(DLS),fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),transmission electron microscope(TEM),zeta-potential measurement and vibrating sample magnetometry(VSM) and MRI.The internalization of uncoated SPIO-NPs,dextran-SPIO-NPs and OCMCS-USPIO-NPs was visualized via prussian blue staining to evaluate the ability of the different SPIO-NPs to escape the macrophage capture.RESULTS The orthogonal experimental design demonstrated that the best technology was as follows: carboxymethyl chitosan molecular weight was 10-20 K,the concentration of OCMCS was 3%,ultrasonic time was 45 min,ultrasonic power was 600 W.FTIR and XRD results confirmed that the successful synthesis of OCMCS-SPIO-NPs.VSM results demonstrated both the modified magnetic Fe3O4 nanoparticles and the uncoated SPIO-NPs were superparamagnetic.The results of characterization also demonstrated that the modification with OCMCS results in a drop in hydrodynamic size,saturated hysteresis(r) while lead to a increase in zeta potential.The prussian blue staining in vitro results indicated the internalization of OCMCS-USPIO-NPs into macrophage was much lower than that of dextran-SPIO-NPs and further lower than SPIO-NPs.CONCLUSION The synthesized OCMCS-USPIO-NPs system is stable with hydrodynamic size less than 50 nm,strong electrostatic repulsion,strong super-paramagnetic and low macrophage uptake.Thus,OCMCS-USPIO-NPs system can be a desirable alternative for MRI contrast agent.