Magnetic Iron Oxide Nano Particles Synthesys and Bio Medical Use

Magnetic Iron Oxide Nano

Particles

Synthesis And Biological Use

N.H.K.S.SenathilakeStudent Index 8558Department of ChemistryUniversity of ColomboSri lanka, August 2009

What is nano technology.?What is nano technology.?

“ The Design, Fabrication and Utilization Of materials,

Structures,

devices and systems

through control matter on the nanometer scale and exploitation of novel phenomena and properties (physical, chemical, biological) at that length scale In At Least One Dimension ”.

Nano particles to Nano structuresNano particles to Nano structures

First generation Nano particles

2D &3D complex Nano Structures

Advanced generation Nano particlese.g.- ligand coated SiO2+Fe3O4 particles

Second generation Nano particlese.g.-Sio2 coated Fe3O4 particles

E.g.-Fe2O3, Au, Ag, polystyrene particles

First generation pure Nano particles (Metal ,metal oxide, polymer etc)

Second generation - chemically modified particle surface

Advanced generation –Further modification to functionalize particles

Nano particle development

Why ferities?-The unique feature of magnetic Why ferities?-The unique feature of magnetic

Nano particlesNano particles Iron oxides having magnetic properties Iron oxides having magnetic properties

with low relaxation time and less with low relaxation time and less toxic to biological systemstoxic to biological systems

Particles that can be controlled by Particles that can be controlled by an external magnetic forcean external magnetic force

Functionalize the particle surface or enclose them in a functioning

nanoparticle to achieve biological, medical benefit

Fe2O3 or Fe3O4Particles-1st generation

SiO2 coated 2nd generation particles

Biologically activemagnetic NanoParticles-advanced generation

Biological applicationsBiological applications of MIONPsof MIONPs

MRI.MRI. A well-known application in the field of diagnosis is A well-known application in the field of diagnosis is the use of MNP s as contrast agents for magnetic the use of MNP s as contrast agents for magnetic resonance imaging (MRI), resonance imaging (MRI),

Better differentiate healthy and pathological tissues and Better differentiate healthy and pathological tissues and to visualize various biological events inside the body.to visualize various biological events inside the body.

Low toxicity and low relaxation timeLow toxicity and low relaxation time

Signal enhancers in MRI imagingSignal enhancers in MRI imaging

Targeted drug delivery and controlled Targeted drug delivery and controlled ReleaseRelease

small sizesmall size Low toxicity to humans, Low toxicity to humans, Can be transported through an Can be transported through an external magnetic field gradient, external magnetic field gradient, penetrating deep into the human penetrating deep into the human tissue. tissue. Attaching a drug to a biocompatible Attaching a drug to a biocompatible MNP carrier, injecting the ferrofluid MNP carrier, injecting the ferrofluid into the bloodstream, and applying into the bloodstream, and applying an external magnetic field to an external magnetic field to concentrate the drug/carrier concentrate the drug/carrier complexes at the target site. complexes at the target site. E.G.- cytotoxic drugs in cancer E.G.- cytotoxic drugs in cancer treatments. treatments.

Drug particles

Magnetit particles

Drug particles

Magnetite particles

HyperthermiaHyperthermia

Based on the ability of MNPs to be heated when a vibrating Based on the ability of MNPs to be heated when a vibrating magnetic field is applied. This characteristic is used to burn magnetic field is applied. This characteristic is used to burn away cancer cells (hyperthermia).away cancer cells (hyperthermia).

cancer cells are more sensitive to temperatures in excess cancer cells are more sensitive to temperatures in excess of 41°C than their normal counterparts. which can of 41°C than their normal counterparts. which can specifically destroy a desired target without deteriorating specifically destroy a desired target without deteriorating healthy surrounding tissue. healthy surrounding tissue.

MIONPs functionalizes to have folic acids (ligand) on the MIONPs functionalizes to have folic acids (ligand) on the surface. This MIONPs binds to folic acid receptors surface. This MIONPs binds to folic acid receptors facilitating the receptor mediated uptake in to malignant facilitating the receptor mediated uptake in to malignant cells. Once the tumor cells engulfed the nanoparticles, then cells. Once the tumor cells engulfed the nanoparticles, then heated the nanoparticles with a rapidly oscillating external heated the nanoparticles with a rapidly oscillating external magnetic field. magnetic field.

Magnetic labelingMagnetic labeling

Great promise as magnetic labels in biosensing with many Great promise as magnetic labels in biosensing with many advantages over conventional labels such as enzymes, fluorescent advantages over conventional labels such as enzymes, fluorescent

dyes, chemiluminescent molecules, and radioisotopesdyes, chemiluminescent molecules, and radioisotopes..

Magnetically labeled entities can be purified, transported, and Magnetically labeled entities can be purified, transported, and detected at the same time.detected at the same time.

E.g.- and cost-effective cancer screening in a specific blood E.g.- and cost-effective cancer screening in a specific blood purification by hemoperfusionpurification by hemoperfusion

Labeling of stem cells to noninvasively monitor the distribution and Labeling of stem cells to noninvasively monitor the distribution and

fate of transplanted stem cells in the human bodyfate of transplanted stem cells in the human body. .

Separation of biological entitiesSeparation of biological entitiesThe attraction between an external magnet and MNP labeled The attraction between an external magnet and MNP labeled componentscomponents

E.g- Isolation of cancer cells in blood samples,E.g- Isolation of cancer cells in blood samples, stem cells in bone marrowstem cells in bone marrow removal of toxins from the human blood removal of toxins from the human blood

(hemoperfusion). (hemoperfusion).

MNPs can be biologically activated to allow the uptake of cells via MNPs can be biologically activated to allow the uptake of cells via endocytotic pathways, thereby allowing certain cellular endocytotic pathways, thereby allowing certain cellular compartments to be specifically addressed. Once taken up, the compartments to be specifically addressed. Once taken up, the desired cellular compartments can be magnetically isolated and desired cellular compartments can be magnetically isolated and accurately studied using proteomic analysis. accurately studied using proteomic analysis.

ChallengesChallenges Two main challenges to make all the above-discussed biomedical Two main challenges to make all the above-discussed biomedical

applications come true:applications come true:

1) A good synthesis route for manufacturing monodisperse MNPs with 1) A good synthesis route for manufacturing monodisperse MNPs with diameters <20nm; diameters <20nm;

2).A good method to functionalize the surface of the nanoparticles2).A good method to functionalize the surface of the nanoparticles

Synthesis of MNPs for biological useSynthesis of MNPs for biological use

Synthesis protocols involves two common stepsSynthesis protocols involves two common steps short nucleation step,short nucleation step, slower growth process on the existing nuclei.slower growth process on the existing nuclei. 1. Micro emulsion 1. Micro emulsion Controlling the very low interfacial tension in precipitation matrix Controlling the very low interfacial tension in precipitation matrix

through the addition of a co surfactant (e.g., an alcohol of through the addition of a co surfactant (e.g., an alcohol of intermediate chain length), intermediate chain length),

2.Co precipitation2.Co precipitation Metal oxide precipitation and a polymerization reaction is carried out Metal oxide precipitation and a polymerization reaction is carried out

at the same time so that the developing particles are trapped inside at the same time so that the developing particles are trapped inside the tiny polymer beads.the tiny polymer beads.

Magnetic nanoparticles for biomedical applications have to be,Magnetic nanoparticles for biomedical applications have to be,

Uniform in sizeUniform in size MonodisperseMonodisperse Smaller sizeSmaller size

Synthesis of MNPs for biological use..ctdSynthesis of MNPs for biological use..ctd

The disadvantages of these water-based methods are that the size uniformity and crystallinity of the MNPs are rather poor, and nanoparticle aggregation is commonly observed.

3.Thermal decomposition (Sun method)3.Thermal decomposition (Sun method)

Involves the high-temperature decomposition (>220°C) of an Involves the high-temperature decomposition (>220°C) of an organic iron precursor in the presence of hydrophobic ligands organic iron precursor in the presence of hydrophobic ligands such as oleic acid These hydrophobic ligands form a dense such as oleic acid These hydrophobic ligands form a dense coating around the nanoparticles, thereby avoiding their coating around the nanoparticles, thereby avoiding their

aggregationaggregation

This method yields uniform and better crystalsThis method yields uniform and better crystals


A major disadvantage in thermal decomposition is that the resulting A major disadvantage in thermal decomposition is that the resulting nanoparticles are soluble only in nonpolar solvents due to their coating nanoparticles are soluble only in nonpolar solvents due to their coating with hydrophobic ligands. with hydrophobic ligands.

Hence, to make MNPs suitable for biological applications, the Hence, to make MNPs suitable for biological applications, the hydrophobic ligand coating needs to be replaced by a hydrophilic hydrophobic ligand coating needs to be replaced by a hydrophilic polymer coating to obtain water soluble particlespolymer coating to obtain water soluble particles


Functionalizing the particleFunctionalizing the particle Chemically active nano particle can then be coated with bio-active Chemically active nano particle can then be coated with bio-active

components such as ligands, antibodies Using the knowledge of components such as ligands, antibodies Using the knowledge of surface chemistry of the particle, surface chemistry of the particle,

Or these particles can be trapped (by co precipitation) in a nano Or these particles can be trapped (by co precipitation) in a nano beads like liposomes, bio degradable polymers which already have beads like liposomes, bio degradable polymers which already have active componentsactive components

Synthesis of MNPs for biological use..ctdSynthesis of MNPs for biological use..ctd CharacterizationCharacterization

1. 1. Energy Filtered Energy Filtered Transmission Electron Transmission Electron MicroscopyMicroscopy

..2. Energy Dispersive2. Energy Dispersive X-ray spectroscopy (EDXS) X-ray spectroscopy (EDXS)

3. Field Emission Transmission 3. Field Emission Transmission Electron Microscopy Electron Microscopy

4. X-ray diffraction (XRD) 4. X-ray diffraction (XRD) analysisanalysis

ReferencesReferences

1. Biomedical applications using magnetic nanoparticles Els Parton 1. Biomedical applications using magnetic nanoparticles Els Parton at el at el

2. Q.A. Pankhurst, at el "Applications of Magnetic Nanoparticles in 2. Q.A. Pankhurst, at el "Applications of Magnetic Nanoparticles in Biomedicine," Biomedicine," Journal of Physics Journal of Physics 36, pp. R167–R181, 2003. 36, pp. R167–R181, 2003.

3. C. Xu, S. Sun, "Monodisperse Magnetic Nanoparticles for 3. C. Xu, S. Sun, "Monodisperse Magnetic Nanoparticles for Biomedical Applications," Biomedical Applications," Polymer InternationalPolymer International, 56, pp. 821–826, , 56, pp. 821–826, 2007 2007

4. T. Hyeon, "Chemical Synthesis of Magnetic Nanoparticles," 4. T. Hyeon, "Chemical Synthesis of Magnetic Nanoparticles," Chemical CommunicationChemical Communication, pp. 927–934, 2007. , pp. 927–934, 2007.

5. S. Sun at el -Nanoparticles," 5. S. Sun at el -Nanoparticles," Journal of the American Chemical Journal of the American Chemical SocietySociety, 126, pp. 273–279, 2004. , 126, pp. 273–279, 2004.

6. R. De Palma et al., "Silane Ligand Exchange to Make 6. R. De Palma et al., "Silane Ligand Exchange to Make Hydrophobic Super-paramagnetic Nanoparticles Water-dispersible," Hydrophobic Super-paramagnetic Nanoparticles Water-dispersible," Chemistry of MaterialsChemistry of Materials, 19, pp. 1821–1831, 2007. , 19, pp. 1821–1831, 2007.

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Magnetic Iron Oxide Nano Particles Synthesys and Bio Medical Use