Fabrication of folic acid magnetic nanotheranostics: An insight on the formation mechanism, physicochemical properties and stability in simulated physiological media

Nanodevices based on magnetite functionalized with folic acid (FA) with improved properties to be employed as theranostics in various types of cancer are here proposed. Two methodologies for FA incorporation were explored aiming to reach suitable loading efficiency as well as adequate stability of nanosystems in physiological media. To this end, simple adsorption and covalent binding of FA and some experimental conditions derived from both procedures were studied. A thorough physicochemical characterization was performed using all the formulations. The mechanism of the interaction between FA and magnetite nanoparticles (MNPs) was elucidated from characterization results supported by theoretical studies using spin-polarized density functional theory (DFT). Both data coincide in that the selective functional group of FA (pteridine group) remained available after FA binding MNPs. Such studies also demonstrated that any of FA carboxylate groups could be available to potentially link other molecule (i.e therapeutic agents). Besides, other issues that are not normally accomplished in reported articles were included; i.e the stability according to two different criteria: size evolution (expressed as hydrodynamic diameter) as a function of time in aqueous media; and the capacity FA retention in PBS, pH = 7.4. Recovered data indicated that the samples are stable at least 15 days in water and 4 h in buffer without significant modifications of their properties. The feasibility of these formulations to interact with simulated physiological fluid was also assayed. The results revealed that protein corona was formed around all the tested formulations leading to more stable nanodevices in terms of their hydrodynamic sizes and size evolution along the time. To complete the theranostic characteristic, Doxorubicin was added to the MNPs@FA by physical adsorption, to provide the therapeutic function. The satisfactory incorporation was verified by FTIR spectroscopy.