76Development of Responsive Nanomagnetic for Delivery of Anticancer Drugs


A new two-step route for the preparation of nano-scaled magnetic chitosan particles has been developed, different from reported one-step in situ preparation and two-step preparation method of reversed-phase suspension, Triton X-100 reversed-phase water-in-oil microemulsion encapsulation method was employed in coating the pre-prepared Fe3O4 nanoparticles with chitosan. Two model anticancer drugs, Doxorubicin (DOX) and Methotrexate (MTX) were loaded effectively to functionalized MNPs through electrostatic interactions. Our developed UV method was applied for simultaneous determination of DOX and MTX. It was concluded that our findings may open the possibilities for pH-responsive targeted delivery of DOX and MTX to the cancerous tissues.

Keywords: Chitosan, Magnetic nanoparticles, Drug delivery, Doxorubicin, Methotrexate.


  • J. Me´ndez, A. Monteagudo, K. Griebenow, Stimulus-responsive controlled release system by covalent immobilization of an enzyme into mesoporous silica nanoparticles, Bioconjugate Chemistry, 23, 698–704, 2012.

  • J. Xi, J. Qin, L.  Fan, Chondroitin sulfate functionalized mesostructured silica nanoparticles as biocompatible carriers for drug delivery, Journal of International Journal of Nanomedicine, 7, 5235–47, 2012.

  • WL. Tung, SH. Hu, DM. Liu, Synthesis of  nanocarriers with remote magnetic drug release control and enhanced drug delivery for intracellular targeting of cancer cells, Acta Biomater, 7, 2873–82, 2011.

  • M. Cao, Z.H. Li, J.L. Wang, W.P. Ge, T.L. Yue, R.H. Li, V.L. Colvin, W.W. Yu, Food related applications of magnetic iron oxide nanoparticles: enzyme immobilization  protein purification and food analysis, Trends in Food Science and Technology, 27, 47–56, 2012.

  • H. Font, J. Adrian, R. Galve, M.C. Estévez, M. Castellari, M. Gratacós-Cubarsí, F. Sánchez-Baeza, M.P. Marco, Immunochemical assays for direct sulphonamide antibiotic detection in milk and hair samples using antibody derivatized magnetic nanoparticles, Journal of Agricultural and Food Chemistry, 56, 736–743, 2008.

  • H.Y. Si, D.P. Li, T.M. Wang, H.L. Zhang, F.Y. Ren, Z.G. Xu, Y.Y. Zhao, Improving the anti-tumor effect of genistein with a biocompatible superparamagnetic drug delivery system, Journal of Nanoscience and Nanotechnology, 10, 2325–2331, 2010.

  • A. Kondo, H. Kamura, K. Higashitani, Development and application of thermosensitive magnetic immunomicrospheres for antibody purification, Applied Microbiology and Biotechnology, 41, 99–105, 1994.

  • M. Faraji, Y. Yamini, M. Rezaee, Magnetic nanoparticles: synthesis, stabilization, functionalization, characterization, and applications, Journal of the Iranian Chemical Society, 7, 1–37, 2010.

  •  X. Zhao, Y. Shi, Y. Cai, S. Mou, Cetyltrimethylammonium bromide-coated magnetic nanoparticles for the preconcepntration of phenolic compounds from environmental water samples, Environmental Science and Technology, 42, 1201–1206, 2008.

  • S. Wittmann, J.P. Majoral, N. Grass Robert, J. Stark Wendelin, O. Reiser, Carbon coated magnetic nanoparticles as supports in microwave-assisted palladium catalyzed Suzuki-Miyaura couplings, Green Process Synthesis, 1, 275–279, 2012.

  • S.T. Selvan, P.K. Patra, C.Y. Ang, J.Y. Ying, Synthesis of silica-coated semiconductor and magnetic quantum dots and their use in the imaging of live cells, Angew. Chem, 119, 2500–2504, 2007.

  • W.L. Xie, J.L. Wang, Immobilized lipase on magnetic chitosan microspheres for transesterification of soybean oil, Biomass Bioenergy, 36, 373–380, 2012.

  • J.K. Oh, D.I. Lee, J.M. Park, Biopolymer-based microgels/nanogels for drug delivery applications, Progress in Polymer Science, 34, 1261–1282, 2009.

  • D.L. Zhao, X.X. Wang, X.W. Zeng, Q.S. Xia, J.T. Tang, Preparation and inductive heating property of Fe3O4–chitosan composite nanoparticles in an AC magnetic field for localized hyperthermia, Journal of  Alloys and Compounds, 477, 739–743, 2009.

  • B. Feng, R.Y. Hong, Y.J. Wu, G.H. Liu, L.H. Zhong, Y. Zheng, J.M. Ding, D.G. Wei, Synthesis of monodisperse magnetite nanoparticles via chitosan–poly(acrylic acid) template and their application in MRI, Journal of  Alloys and Compounds, 473, 356–362, 2009.

  • S. Akgöl, Y. Kaçar, A. Denizli, M.Y. Arýca, Hydrolysis of sucrose by invertase immobilized onto novel magnetic polyvinylalcohol microspheres, Journal of Agricultural and Food Chemistry, 74, 281–288, 2001.

  • A.H. Li, H.Y. Zhang, X. Zhang, Q. Wang, J.S. Tian, Y. Li, J.L. Li, Rapid separation and immunoassay for low levels of Salmonella in foods using magnetosomeantibody complex and real-time fluorescence quantitative PCR, Journal of Separation Science, 33, 3437–3443, 2010.  [18] Q. Gao, D. Luo, M. Bai, Z.W. Chen, Y.Q. Feng, Rapid determination of estrogens in milk samples based on magnetite nanoparticles/polypyrrole magnetic solidphase extraction coupled with liquid chromatography-tandem mass spectrometry, Journal of Agricultural and Food Chemistry, 59, 8543–8549, 2011.

  • J.S. Pang, A.H. Deng, J. Chen, L.B. Mao, J. Zhu, Determination of migration quantity of Cr, Ni, Cd, Pb and As in food containers by magnetic carbon-coated iron nanoparitcles separation/enrichment-inductively coupled plasma atomic emission spectrometry, Journal of Analytical Chemistry, 39, 1363–1367, 2011.

  • H. Wang, J. Ding, X.B. Du, X. Sun, L.G. Chen, Q.L. Zeng, Y. Xu, X.P. Zhang, Q. Zhao, L. Ding, Determination of formaldehyde in fruit juice based on magnetic strong cation-exchange resin modified with 2,4-dinitrophenylhydrazine, Journal of Agricultural and Food Chemistry, 131, 380–385, 2012.

  • N.A. Kalkan, S. Aksoy, E.A. Aksoy, N. Hasirci, Adsorption of reactive yellow 145 onto chitosan coated magnetite nanoparticles, Journal of Applied Polymer Science, 124, 576–584, 2012.

  • N.D. Cuong, T.T. Hoa, D.Q. Khieu, T.D. Lam, N.D. Hoa, N. Van Hieu, Synthesis, characterization, and comparative gas-sensing properties of Fe2O3 prepared from Fe3O4 and Fe3O4-chitosan, Journal of  Alloys and Compounds, 523, 120–126, 2012.

  • J. Zhi, Y. Wang, Y. Lu, J. Ma, G. Luo, In situ preparation of magnetic chitosan/ Fe3O4 composite nanoparticles in tiny pools of water-in-oil microemulsion, Reactive and Functional Polymers, 66, 1552–1558, 2006.

  • A. Tomitaka, A. Hirukawa, T. Yamada, S. Morishita, Y. Takemura, Biocompatibility of various ferrite nanoparticles evaluated by in vitro cytotoxicity assays using HeLa cells, Journal of Magnetism and Magnetic  Materials, 321, 1482–1484, 2009.

  • C.I. Covaliu, D. Berger, C. Matei, L. Diamandescu, E. Vasile, C. Cristea, V. Ionita, H. Iovu, Magnetic nanoparticles coated with polysaccharide polymers for potential biomedical applications, Journal of Nanoparticle Research, 13, 6169–6180, 2011.