Effects of surface modifications on the physicochemical properties of iron oxide nanoparticles and their performance as anticancer drug carriers

Surface of iron oxide nanoparticles were modified with citric acid (CA), chitosan (CS) and folic acid conjugated chitosan (FA-g-CS), respectively. Their physicochemical properties, doxorubicin loading capacity, drug release patterns and in vitro cytotoxicity were comparatively studied. [Display omitted] The feature of the surface coating can affect important properties of iron oxide nanoparticles (IONPs), it is therefore critical for further understanding how these materials react to physiological conditions, which is still needed to fully exploit the potential of IONPs for their theranostic applications. In this work, we prepared IONPs which surface were modified with citric acid (CA), chitosan (CS) and folic acid conjugated chitosan (FA-g-CS), respectively. Their physicochemical properties were investigated using FT-IR, TEM, powder XRD, VSM, TGA, DLS and zeta potential. We found that CA-IONP dispersion was composed of monocrystalline particles while CS-IONP and FA-g-CS-IONP were composed of polycrystalline aggregates. All IONPs retained the crystalline structure of magnetite and exhibited the superparamagnetic behavior. Their saturation magnetization decreased with the increase in the amount of their organic coatings. Their drug loading capacities, drug release patterns and in vitro anticancer efficiencies were studied by using doxorubicin (DOX) as a model drug. DOX@CS-IONP and DOX@FA-g-CS-IONP exhibited lower drug loading while showing higher water dispersity when compared with DOX@CA-IONP. All IONPs were surface charged and they tended to agglomerate in medium with high pH value and ionic strength. In the presence of chitosan or FA-g-CS coatings, their DOX release rate was slowed down compared with that of DOX@CA-IONP. Unloaded IONPs exhibited nearly no cytotoxicity on both cancer cells and normal cells in the presence of chitosan and FA-g-CS when compared with CA-IONP which presented high cytotoxicity. However, DOX@FA-g-CS-IONP showed significantly cytotoxicity on folate receptors (FRs) positive breast cancer cells while exhibiting nearly no cytotoxicity on FRs negative normal cells. Results presented in this study were valuable to the design and fabrication of IONPs-based system for better theranostic applications.