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Outline

Biomedical Applications of Magnetic Nanoparticles

2009

Abstract

The thesis focuses on the specific design of multifunctional magnetic nano-carriers for different biomedical areas. Different shapes of core/shell bi-magnetic nanoparticle have been synthesized by seedmediated growth, and their structural and magnetic properties have been studied. The experimental results showed that core/shell nanoparticles have a higher specific absorption rate compared to the core ones. For drug delivery application, the surface of the magnetic nanoparticles is functionalized using different techniques (Diels-Alder reaction and layer-by-layer technique). More precisely, a novel bi-functional thermo-responsive system, which consists of core/shell bi-magnetic nanoparticles with furan surface functionality, is bonded with N-(2-Carboxyethyl)maleimide through Diels-Alder reaction. The chemotherapeutics doxorubicin is attached onto the surface of the nanocarriers, and a high loading efficiency of 92% is obtained. This system with high responsiveness to a high frequency external alternating magnetic field shows a very good therapeutic efficiency in hyperthermia and drug release at relatively low temperatures (50 °C). On the other hand, a switch-controlled drug release is realized by coating the core/shell bi-magnetic nanoparticle with a pH-and thermo-responsive polymer shell. Doxorubicin is loaded onto the surface of the last coating layer, and a high loading efficiency is obtained. The nano-carriers are characterized with FTIR, dynamic light scattering, Zeta potential, In vitro hyperthermia, and vibrating sample magnetometry. The in vitro drug release experiments confirm that a small amount of doxorubicin is released at body temperature and physiological pH, whereas a high drug release is obtained at acidic tumor pH under hyperthermia conditions (43 °C). The core/shell bi-magnetic nano-carriers facilitate controllable release of doxorubicin as effect of induced thermo-and pHresponsiveness of the polymer when are subjected to an high-frequency alternating magnetic field at acidic pH; thereby the drug release rate is controlled using on-off cycles of the applied field. iii KURZFASSUNG Diese Arbeit befasst sich mit der speziellen Gestaltung von multifunktionalen magnetischen Nanopartikeln für diverse biomedizinische Anwendungen. Verschiedene Formen der Kern/Schale-bimagnetischen Nanopartikel wurden durch die "seed-mediated growth" Methode synthetisiert, und die strukturellen und magnetischen Eigenschaften dieser Formen untersucht. Die Versuchsergebnisse haben gezeigt, dass die Kern/Schale-Nanopartikel eine höhere spezifische Energiea als reine Kern Partikel haben. Für die Drug Delivery Anwendung wird die Oberfläche der magnetischen Nanopartikel auf unterschiedlichen Wege (Diels-Alder-Reaktion und Layer-by-Layer-Verfahren) funktionalisiert. Dazu wurde an ein neuartiges bifunktionelles thermosensitives System, welches aus furanbeschichteten Kern/Schale bi-magnetischen Nanopartikel besteht, N-(2-Carboxyethyl) maleimid durch Diels-Alder Reaktion angebunden. Mit der Anbindung des chemotherapeutischen Doxorubicins an die Oberfläche der nano-carriers wurde ein hohe Beladungsgrad von 92% erzielt. Dieses System mit hoher Ansprechempfindlichkeit auf hochfrequente äußere magnetische Wechselfelder zeigt eine sehr gute therapeutische Wirksamkeit in der Hyperthermie und als Drug-Delivery-System bei relativ niedrigen Temperaturen (50 °C). Ein schaltbare Wirkstofffreisetzung wird durch Beschichtung der Kern/Schale bimagnetischen Nanopartikel mit einer pH-und temperaturempfindlichen Polymerschicht ermöglicht. Mit der Anbringung des Doxorubicins auf die Oberfläche der letzten Beschichtung wurde eine hohe Beladungseffizienz erhalten. Diese System wird mittels dynamischer Lichtstreuung, FT-IR-, In-vitro-Hyperthermie, UV/Vis-und Fluoreszenz-Spektroskopie, sowie Zetapotential-Messungen charakterisiert. Die in vitro Wirkstofffreisetzungsversuche bestätigen, dass eine kleine Menge von Doxorubicin bei Raumtemperatur und physiologischen pH freigesetzt wird, während eine hohe Wirkstofffreisetzung bei sauren pH-Werten in Tumoren unter Hyperthermi Bedingungen (43 ° C) erhalten wird. Die Kern/Schale bimagnetischen Nanopartikel erleichtern die Freisetzung von Doxorubicin infolge der induzierten thermound pH-Ansprechempfindlichkeit des Polymers, wenn sie in einem hochfrequenten magnetischen Wechselfeld einem sauren pH-Wert ausgesetzt werden. Dadurch wird die Arzneimittelfreisetzungsrate anhand on-off-Zyklen des angelegten Feldes gesteuert. iv

FAQs

sparkles

AI

What loading efficiency for doxorubicin was achieved with core/shell bi-magnetic nanoparticles?add

The study reports a high loading efficiency of 92% for doxorubicin attached to the nanoparticles.

How does zinc substitution affect the magnetic properties of nanoparticles?add

Increased zinc substitution resulted in Ms values growing from 44.9 emu/g to 61.5 emu/g before declining to 47.1 emu/g at higher concentrations.

What is the observed SAR for the synthesized core/shell magnetic nanoparticles?add

The specific absorption rate (SAR) achieved for the best-performing nanoparticles was noted to be twice that of the core, indicating enhanced magnetic properties.

Which technique is used to functionalize magnetic nanoparticles in the study?add

Functionalization was accomplished using Diels-Alder reaction techniques to ensure efficient drug loading and responsiveness.

What temperature range was effective for hyperthermia treatment according to the findings?add

Hyperthermia treatments are noted to be effective when body tissue is exposed to temperatures between 41 °C and 50 °C.

References (186)

  1. Introduction ..........................................................................................................................................
  2. Theory and background ........................................................................................................................ 2.1 Magnetic nanoparticles ................................................................................................................
  3. 1.1 Introduction ..........................................................................................................................
  4. 1.2 Synthesis of Magnetic Nanoparticles ....................................................................................
  5. Nanomagnetism ....................................................................................................................
  6. 1.4 Application in life science....................................................................................................
  7. 2 Diels-Alder reaction ....................................................................................................................
  8. 2.1 Introduction ........................................................................................................................
  9. 2.2 Reaction mechanism ...........................................................................................................
  10. 2.3 Synthetic application ...........................................................................................................
  11. 3 Layer-by-layer Assembly .............................................................................................................
  12. 3.1 Introduction ........................................................................................................................
  13. Assembly Concept ...............................................................................................................
  14. 3 Experimental section ..........................................................................................................................
  15. Part I ............................................................................................................................................
  16. 1.1 Synthesis of ZnxCo1-xFe2O4 nanoparticle seeds ....................................................................
  17. 1.2 Synthesis of ZnxCo1-xFe2O4@MnFe2O4 nanoparticles ..........................................................
  18. 1.3 Preparation of hydrophilic ZnxCo1-xFe2O4@MnFe2O4 Nanoparticles ...................................
  19. 2 Part II ...........................................................................................................................................
  20. 2.1 Synthesis of Zn0.4Co0.6Fe2O4 nanoparticle seeds..................................................................
  21. 2.2 Synthesis of Zn0.4Co0.6Fe2O4@xZn0.4Mn0.6Fe2O4 nanoparticles ............................................
  22. 3 Part III ..........................................................................................................................................
  23. 3.1 Synthesis of truncated octahedron Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 nanoparticles .........
  24. 3.2 Conjugation of DOX to Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 nano-carriers via thermo- responsive switch ................................................................................................................
  25. 4 Part IV ..........................................................................................................................................
  26. 4.1 Synthesis of spherical Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 nanoparticles ..............................
  27. 4.2 LBL coating of core/shell magnetic nanoparticles ..............................................................
  28. 4.3 Doxorubicin loading onto the last layer (PAA) of the coating ............................................
  29. 3.5 Characterization of core/shell magnetic nanoparticles and its functionalization ......................
  30. 5.1 X-ray diffraction (XRD) ........................................................................................................
  31. 5.2 Transmission electron microscopy (TEM) ...........................................................................
  32. 5.3 X-ray photoelectron spectroscopy (XPS) ............................................................................
  33. 5.4 Dynamic light scattering (DLS) ............................................................................................
  34. 5.5 Fourier transform infrared spectroscopy (FT-IR) ................................................................
  35. 5.6 Thermogravimetry (TG) ......................................................................................................
  36. 5.7 Zeta potential ......................................................................................................................
  37. 5.8 Vibrating sample magnetometery (VSM) ...........................................................................
  38. 9 In vitro hyperthermia ..........................................................................................................
  39. 5.10 In vitro drug release assay...................................................................................................
  40. 5.11 Cytotoxicity assay ................................................................................................................
  41. Results and discussions .......................................................................................................................
  42. Part I ............................................................................................................................................
  43. 1.1 Effect of Zn substitution on the structural properties of magnetic nanoparticles .............
  44. 1.2 Effect of Zn substitution on the magnetic properties of magnetic nanoparticles ..............
  45. 2 Part II ...........................................................................................................................................
  46. 2.1 Effect of experimental parameters on the structural properties of magnetic nanoparticles .............................................................................................................................................
  47. 2.2 Effect of experimental parameters on the magnetic properties of magnetic nanoparticles . .............................................................................................................................................
  48. 3 Part III ..........................................................................................................................................
  49. 3.1 Structural characterizations of truncated octahedron magnetic nanoparticles ................
  50. 3.2 Magnetic properties of truncated octahedron magnetic nanoparticles ............................
  51. 3.3 Cytotoxicity assay of functionalized magnetic nanoparticles .............................................
  52. 3.4 Conjugation of doxorubicin to functionalized magnetic nanoparticles ..............................
  53. 3.5 Doxorubicin release profiles ...............................................................................................
  54. 4 Part IV ..........................................................................................................................................
  55. 4.1 Structural characterizations of spherical magnetic nanoparticles .....................................
  56. 4.2 Magnetic properties of spherical magnetic nanoparticles .................................................
  57. 4.3 Cytotoxicity Assay of nanoparticles ....................................................................................
  58. 4.4 Loading of doxorubicin with coated magnetic nanoparticles .............................................
  59. 4.5 Doxorubicin release profile .................................................................................................
  60. Summary and conclusion ....................................................................................................................
  61. Appendix .....................................................................................................................................................
  62. M. Hammad, V. Nica, R. Hempelmann On-Command Controlled Drug Release by Diels-Alder Reaction Using Bi-Magnetic Core/Shell Nano- carriers. (Submitted to Colloids and Surfaces B: Biointerfaces)
  63. M. Hammad, V. Nica, R. Hempelmann On-Off Switch Controlled Doxorubicin Release from Thermo-and pH-Responsive Coated Bi-Magnetic Nano-Carriers. (Submitted to Journal of Nanoparticles Research)
  64. M. Hammad, V. Nica, R. Hempelmann Synthesis and characterization of bi-magnetic core/shell for hyperthermia applications. (Submitted to IEEE Transactions on Magnetics)
  65. M. Hammad, V. Nica, R. Hempelmann Enhanced Specific Absorption Rate of Bi-magnetic Nanoparticles for Heating Applications. (In preparation) A3.2 Conference proceedings M. Hammad and R. Hempelmann Functionalization of Magnetic Nanoparticles by Diels-Alder Reaction.
  66. German Ferrofluid Workshop, 15 -17 July 2015, Rostock, Germany.
  67. V. Nica, M. Hammad, M.L. Garcia Martin, R. Hempelmann Shape Anisotropic Bi-magnetic Nanoparticles for Application in Hyperthermia. TIM15-16 Physics Conference, 26 -28 May 2016, Timisoara, Romania.
  68. M. Hammad, V. Nica, and R. Hempelmann Synthesis and Characterization of Bi-magnetic Core/Shell for Hyperthermia Applications.
  69. European Magnetic Sensors and Actuators, 12 -15 July 2016, Torino, Italy.
  70. V. Nica, M. Hammad, M.L. Garcia Martin, R. Hempelmann Influence of the Surfactants on the Physiochemical Properties of Hard/Soft Bi-magnetic Nanoparticles.
  71. European Magnetic Sensors and Actuators, 12 -15 July 2016, Torino, Italy.
  72. V. Nica, M. Hammad, M.L. Garcia Martin, R. Hempelmann On-Command Multifunctional Bi-magnetic Core-Shell Nanoparticles for Biomedical Applications Advances in Functional Materials (AFM 2016), 8 -11 Augst 2016, Jeju, South Korea V. Nica, M. Hammad, M.L. Garcia Martin, R. Hempelmann Enhanced Specific Absorbtion Rate of Exchange Coupled Bi-Magnetic Nanoparticles for High Frequency Electromagnetic Absorption Europe-Korea Conference on Science and Technology (EKC 2016), 27 -30 July 2016, Berlin, Germany A5. REFERENCES
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