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176   Computational Modeling in Biomedical Engineering and Medical Physics


                The concern that, however, mounts is that increasingly more nanoparticles are produced
                to meet the rapidly growing requirements of nanomedicine (Singh et al., 2010).
                   The usage of SPIONs in MDT could be the menace of their aggregation for rea-
                son of their surface to volume ratio. In an external, permanent, intense magnetic field,
                SPIONs get magnetized and each particle may influence (alter) the local magnetic
                field. This may produce dipole dipole interactions between particles, so that the par-
                ticles get aligned along the force lines of the external PM (Markides et al., 2012).
                   Moreover their nanometric size (large surface area causes increased reactivity and
                enhances the tendency to diffuse through the biological membranes which can cause
                cellular stress) could have the potential to induce cytotoxicity, manifested by impaired
                cell function: mitochondria, nucleus, DNA. In addition, if the particles clump or
                absorb plasma proteins, they are rapidly removed from the bloodstream by macro-
                phages and can no longer reach the cells aim. The coating and functionalization of the
                particles are then decisive for their applicability and their degree of biocompatibility
                with the human organism (Singh et al., 2010; Xu and Sun, 2013).

                Superparamagnetic iron oxide nanoparticles synthesis, coating, and
                functionalization
                The iron oxide core of the SPION can be chemically synthesized through various
                methods: standard synthesis by coprecipitation (Marinin, 2012), reactions in con-
                strained environments (Singh and Lillard, 2009), polyol method (Ali et al., 2016), flow
                injection synthesis (Salazar-Alvarez et al., 2006), sonolysis (for MNPs used simulta-
                neously to diagnose and treat diseases) (Kudr et al., 2017) or thermolysis (used for for-
                mation of iron oxide MNPs from their organometallic precursors) (Lin et al., 2012).
                Uncoated MNPs poses low solubility and may precipitate (if not small enough) and
                also have high rates of cloistering in physiological conditions, which may lead to blood
                vessels clogging in clinical applications. Therefore they are clad with a superficial over-
                lay aimed to ensure efficiency in clinical applications and to improve their biocompati-
                bility, that is, the ability to achieve an appropriate host reaction in a particular
                situation, and biodistribution, that is, to track the travel of the compounds of interest
                in an experimental animal or human subject (LexInnova, 2020).
                   SPIONs coating with polymers for drug delivery preserves their magnetic proper-
                ties (Mahmoudi et al., 2011) and provides for the most common protection against
                their oxidation (Faraji and Wipf, 2009; Singh and Lillard, 2009). A major challenge,
                at this stage, is the uniform size distribution of the coating, a high level of monodisper-
                sion, that is, uniformity, and composition homogeneity.
                   The functionalization of the SPIONs surface using polymer coating with biocompat-
                ible molecules, such as dextran, dendrimers, polyethylene glycol, or albumin, aims at
                binding complex biological molecules, such as drugs, antibodies, hormones, or peptides,
                with materials such as silicone, dextran,and pegylated citrate (Musielaka et al., 2009), which
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