چكيده به لاتين
Iron oxide nanoparticles (with molecular formula Fe3O4), and its applications in different scientific scopes has been highly noticed by the researchers in recent years due to having disinguished pHysical and chemical properties. As the first and foremost feature, superparamagnetic behaviour of the iron oxide nanoparticles has provided an approriate opportunity for the pHysical control of the particles in different applications. Moreover, the capability of the iron oxide nanoparticles for surface functionalization with the organic and inorganic compounds, and the forrmation of hybrid nanostructures with modified properties, and also structural stability against increase in the temperature are other advantages of the iron oxide nanoparticles. In this thesis, these great excellences have been considered in two important research scopes; 1) design and preparation of magnetic catalytic systems, and 2) design and preparation of magnetic drug delivery systems.
Protein ingredients have been highly noticed and widely used in the structure of the novel Pharmaceutical compounds because they are biologically active and capable to deal with the living cells. Hence, they have deeply affected the therapeutic properties of the chemical drugs and nanomedicines, specially in recent decades. In this regard, both synthetic and biosynthetic proteins (like peptides and antibodies) are used for the enhancement of cell-penetration and increasing the targeting in cell attachment. The medicinal compounds containing a chemical drug plus a protein structure are typically called “Pharmaceutical Conjugates”.
In this thesis, the efficiency of the iron oxide nanoparticles is investigated from two different aspects;
1) As a suitable basis for preparation of the heterogeneous magnetic catalytic systems in nanoscale, functionalized with the organic and inorganic compounds: Since, synthesis of the Pharmacutical conjugates almost follows a peptide/amide bond formation approach, design and preparation of the novel heterogeneous catalytic systems as an appropriate alternative for traditional coupling reagents is of high importance. Also, design and preparation of the same catalytic systems as the alternatives for the chemcial reducing agents, which are used for providing the active chemcal sites in the structure of the proteins with native architecture (like antibodies), is important because of providing high convenience in the separation process and can be suitably replaced to the conventional methods such as dialysis. In summary, in this thesis, the surface of iron oxide nanoparticles is functionalized with isothiazolone and dithiothreitol, and the reulted catalytic systems are applied in the chemical reactions including amid/peptide bond formation and partial reduction of disulfide bonds in the structure of
herceptin (TRA, Her 2) antibody. Ultimately, an effective conjugation between levofloxacin (as an anti-infection drug) and a six-membered peptide sequence (as a cell-penetrating agent) has been synthesized by applying the prepared magnetic catalytic systems. Concisely, it has been observed that the growth inhibition effect of the synthesized Pharmaceutical conjugate on the bacteria cells is more than the individual levofloxacin.
2) As a suitable basis for preparation of the magnetic drug delivery systems, hybridized to the polymeric strands and functionalized with the protein compounds: One the possible strategies in targeted drug delivery is using of an external magnetic field for the direction of the magnetic particles to the target tissue in the body’s internal environment. Moreover, possible synergistic effects in cell-penetration and controlled drug release processes resulting in reduction of minimum effective dosage (MED) and increase in maximum tolerated dosage (MTD) levels (known as therapeutic window), is a great potential in the magnetic drug delivery systems. In this thesis, nanoscale drug delivery systems based on the iron oxide nanoparticles as the magnetic core and polyvinyl alcohol (PVA) as a suitable matrix (as shell) for efficient encapsulation and controlled release of the drug molecules have been designed and suggested. Briefly, the obtained results from in vitro and in vivo studies have revealed that the synergies between the temperature raise (controlled via plasmonic effect of the gold nanoparticles) and acidic conditions, result in a significant growth inhibition over the MCF-7 breast cancer, Caov-4 ovary cancer, and both Gram-positive and –negative bacterial cells.
