Review Article A REVIEW ON BIOMEDICAL APPLICATIONS & SYNTHESIS OF IRON OXIDE NANO PARTICLES Krithika mohanraj 1*, Lone Saquib 2

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1 ISSN: X CODEN: IJPTFI Available through Online Review Article A REVIEW ON BIOMEDICAL APPLICATIONS & SYNTHESIS OF IRON OXIDE NANO PARTICLES Krithika mohanraj 1*, Lone Saquib Department of Biomedical Engineering, Bharath University, Chennai. krithika.mohanraj@gmail.com Received on Accepted on Abstract Iron oxide nanoparticles with appropriate surface chemistry exhibit interesting properties that can be exploited in a variety of biomedical applications such as tissue repair, hyperthermia, targeted drug delivery, magnetic resonance imaging contrast enhancement and in cell separation. This review focuses on the recent development and various strategies in preparation, surface functionalization and magnetic properties of iron oxide nanoparticles and their corresponding application briefly. In order to implement the various biomedical applications, the particles should have properties such as high magnetic saturation, stability, biocompatibility and interactive functional moieties at the surface. Moreover, the surface of iron oxide nanoparticles could be modified by coating organic materials or inorganic materials such as polymers, silica, bio molecules etc. The major challenges in synthesis and surface functionalization of iron oxide nanoparticles are considered. Keywords: Iron oxide Nanoparticles, MRI, Hyperthermia, Drug delivery, Magnetic saturation Introduction The use of nanoparticles offer many advantages due to their unique size and physical properties. Nanoparticles have been used to deliver drugs to target tissues and to increase stability against degradation by enzymes. The super paramagnetic nanoparticles is the one, which can be manipulated by an external magnetic field to target the tissue[1]. Based on their unique physical, chemical, thermal, and mechanical properties, nanoparticles offer a high potential for several biomedical applications, such as targeting tool, magnetic field-guided nanocarriers for localizing therapeutic agents, tissue repair, magnetofection, magnetic resonance imaging ; hyperthermia [2,3]. Special surface coating of the IJPT Sep-2015 Vol. 7 Issue No Page 3256

2 magnetic particles make it non-toxic, biocompatible and allow a targetable delivery with particle localization in a specific area. Nanoparticles can bind to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to any organ, tissue or tumour using an external magnetic field or can be heated using external magnetic field in case of hyperthermia. Particles are injected into a certain part of the body and a magnet was placed outside to the point of injection, such that the particles were retained at the location of the magnet, Moreover, by placing the magnet in the vicinity of some organs,it was possible to increase the concentration of the drugs at that tissue. Another field of medical applications where magnetic nanoparticles are very useful is magnetic resonance imaging (MRI).Because of their tendency to accumulate with different tissue compositions, one can use magnetic nanoparticles as contrast agents for the localization and diagnostics of various tumors[4]. Magnetic resonance imaging: MRI is one of the non-invasive medical diagnostic techniques. MRI of normal and abnormal tissues are difficult to differentiate therefore, specific exogenous contrast agents are needed to increase the contrast and to obtain higher resolution and sensitivity. SPIONs have been extensively used as contrast agents for MRI of tumours targeting probes. There are two important criteria to use SPIONs as MRI imaging probes.[15,16] The super paramagnetic SPIONs exhibit a high magnetization when an external magnetic field is applied the magnetization becomes zero when the external magnetic field is removed. They provide the negative (dark) contrast by enhancing relaxivity of water protons for MR images. Targeting ligands such as antibodies, polymers, proteins, peptides, DNA, RNA can be introduced on the surrounding magnetic nanoparticles to improve the target-specific tumors [5,6] Hyperthermia: Multifunctional SPIONs have been used in hyperthermia treatment of cancer. In this therapy, the Nano Particles are exposed to an oscillating magnetic field and heat is generated to kill the tumor cells due to the two following mechanisms that depend on the size of the particles: Brownian modes ( For Nanoparticles < 100 nm in diameter, heat produced due to friction between oscillating particles) and Neél modes ( For larger particles, heat produced due to the rotation of the magnetic moment with each field oscillation) [7]. IJPT Sep-2015 Vol. 7 Issue No Page 3257

3 Drug delivery systems: The surface of SPIONs has been modified to incorporate the drugs such as doxorubicin, one of the clinically approved anticancer drugs for breast cancer. The water insoluble drug, doxorubicin was loaded into the SPIONs by double emulsion solvent evaporation method and released slowly over 2 weeks under in vitro conditions in breast and prostate cancer cell lines. Chen et al. described a method to bind doxorubicin covalently to Fe3O4 SiO2 core-shell via an amide bond, where the active COOH group on nanoparticles reacted with the NH2 group of Dox molecules [8]. The Doxloading was 86.5% and the release behaviour was studied under low ph conditions in the presence of protease. Hyeon and coworkers have developed uniform mesoporous silica NanoParticles decorated with dye and multiple magnetite SPIONs for MRI, fluorescence imaging and drug delivery. This system has successfully enabled the delivery of DOX into the tumour sites[9]. RNA delivery: RNA-based therapeutics such as small interfering RNA (sirna) and microrna (mirna) provide a promising strategy to treat cancer by targeting the specific proteins involved in the mechanism of proliferation, invasion, anti-apoptosis, drug resistance, and metastasis. NPs complexed with polycations and attached to cholesterol groups or conjugated with cell-surface receptors are commonly used for in vivo delivery of therapeutic sirnas. The cholesterol groups can enhance their stability before systemic delivery. Furthermore, the receptor-mediated cell uptake and release by endosomes would enable for the targeted delivery of the sirnas [10]. Synthesis methods: Methods for preparing iron oxide nanoparticles include thermal decomposition microemulsion, and co precipitation method. The most conventional method for obtaining Fe3O4 or Fe2O3 is by co-precipitation. This method consists of mixing ferric and ferrous ions in a 1:2 molar ratio in highly basic solutions at room temperature or at elevated temperature[11]. This method offer a low-temperature alternative to conventional powder synthesis techniques in the production of nanoparticles. It can produce fine, high-purity particles of single and multicomponent metal oxides. The size and shape of the iron oxide Nano Particles depends on the type of salt used such as chlorides, sulfates, nitrates, etc., the ferric and ferrous ions ratio, the reaction temperature, the PH value, ionic strength of the media, and the other reaction parameters (e.g. stirring rate, dropping speed of basic solution) are important. Surfactants act as protecting IJPT Sep-2015 Vol. 7 Issue No Page 3258

4 agent for controlling particle size and stabilizing the colloidal dispersions. Additionally, the disadvantage of these aqueous solution syntheses is that the high ph value of the reaction mixture[12][20]. High temperature methods Monodisperse particles with significant size control, and high crystallinity, can be achieved using high temperature methods. In this method, iron complexes are decomposed in the presence of surfactants and organic solvents. The high temperatures used in this method, and the nature of the solvent, result in the SPIONS having suitable size, and size distribution, with high crystallinity [13]. SYNTHESIS METHODS ADVANTAGES DISADVANTAGES Co precipitation Rapid synthesis with high yield Problem of oxidation and aggregation Hydrothermal reaction Narrow size distribution and good control, scalable Long reaction times High temperature Good control of size and shape, Furthers steps needed to obtain water decomposition High yield stable suspension Microemlusion Control of particle size Poor yield and large amounts of solvent required, excess of surfactant to eliminate There is a variety of analysis tools to characterise spions. It is important to characterise spions, since its properties mainly influence the application of spions. For any biological application, tests such as biocompatibility, toxicity and efficacy, needs to be considered. The most general properties need to be analysed are the physical (size, shape, chemical phases) and magnetic properties.[17,18,19] Conclusion For biological and biomedical applications, magnetic iron oxide nanoparticles are the primary choice because of their biocompatibility, superparamagnetic behaviour and chemical stability. Magnetic nanoparticles loaded with IJPT Sep-2015 Vol. 7 Issue No Page 3259

5 chemotherapeutic drug targeting the tumor site can not only eliminate adverse side effects, but may also pave the way for bringing a more effective and specific method for eradicating cancer and many other complex diseases. Magnetic nanoparticles in cancer detection and treatment have the potential to replace highly invasive conventional cancer detection and treatment. Co-precipitation method is one of the convenient and cheap methods as it has the potential to meet the increasing demand for the direct preparation of well dispersed Fe3O4 nanoparticles. References: 1. Faraji, M.; Yamini, Y.; Rezaee, M. Magnetic Nanoparticles: Synthesis, Stabilization, Functionalization, Characterization, and Applications. J. Iran. Chem. Soc. 2010, 7, Prijic, S.; Sersa, G. Magnetic nanoparticles as targeted delivery systems in oncology. Radiol. Oncol.2011, 45, Hong, R.Y.; Pan, T.T.; Han, Y.P.; Li, H.Z.; Ding, J.; Sijin, H. Magnetic field synthesis of Fe3O4 nanoparticles used as a precursor of ferrofluids. J. Magn. Magn. Mater. 2007, 310, Arbab, A.S.; Bashaw, L.A.; Miller, B.R.; Jordan, E.K.; Lewis, B.K.; Kalish, H.; Frank, J.A. Characterization of biophysical and metabolicproperties of cells labeled with superparamagnetic ironoxide nanoparticles and transfection agent for cellular MR imaging. Radiology 2003, 229, Pankhurst, Q.A.; Connolly, J.; Jones, S.K.; Dobson, J. Applications of magnetic nanoparticles inbiomedicine. J. Phys. D. Appl. Phys. 2003, 36, R167 R Dorniani, D.; Bin Hussein, M.Z.; Umar Kura, A.; Fakurazi, S.; Halim Shaari, A.; Ahmad, Z. Preparation of Fe3O4 magnetic nanoparticles coated with gallic acid for drug delivery. Int. J. Nanomed. 2012, 7, Molecules 2013, Kim, D.K. Characterization and MRI study of surfactant-coated superparamagnetic nanoparticles administrated into the rat brain. J. Magn. Magn. Mater. 2001, 225, Jun YW, Seo JW, Cheon J. Nanoscaling laws of magnetic nanoparticles and their applicabilities in biomedical science. Acc. Chem. Res. 2008; 41: Jain TK, Morales MA, Sahoo SK, Leslie-Pelecky DL, Labhasetwar V. Iron oxide nanoparticles for sustained delivery of anticancer agents. Mol. Pharmaceutics 2005; 2: IJPT Sep-2015 Vol. 7 Issue No Page 3260

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7 18. Rajkumar B., Vijay Kalimuthu B., Rajkumar R., Santhakumar A.R., "Proportioning of recycled aggregate concrete", Indian Concrete Journal, ISSN : , 79(10) (2005) pp Vijayaprakash S., Langeswaran K., Jagadeesan A.J., Rveathy R., Balasubramanian M.P., "Protective efficacy of Terminalia catappa L. leaves against lead induced nephrotoxicity in experimental rats", International Journal of Pharmacy and Pharmaceutical Sciences, ISSN : , 4(S3) (2012) pp Lartigue L, Innocenti C, Kalaivani T, Awwad A, Duque MdMs, Guari Y, Larionova J, Guérin C, Montero J-LG, Barragan-Montero V, Arosio P, Lascialfari A, Gatteschi D, Sangregorio C. Water-dispersible sugar-coated iron oxide nanoparticles. An Evaluation of their relaxometric and magnetic hyperthermia properties. J. Am. Chem. Soc. 2011; 133: Corresponding Author: Krithika mohanraj *, Bharath University, Chennai. IJPT Sep-2015 Vol. 7 Issue No Page 3262