Biomedical applications based on Biomedical applications based on - PowerPoint PPT Presentation

“Biomedical applications based on Biomedical applications based on “ magnetic nanoparticles” ” magnetic nanoparticles R. Fernández-Pacheco 1 , C. Marquina 2 , D. Serrate 2 and J.G Valdivia 1 M. Gutierrez 1 and M.R. Ibarra 1,2 1 Instituto de Nanociencia de Aragón, Edificio Interfacultades II, Zaragoza (Spain) 2 Instituto de Ciencia de Materiales de Aragón (CSIC/Universidad de Zaragoza), Facultad de Ciencias, Zaragoza (Spain Constanta 2005

OUTLINE OF THE TALK OUTLINE OF THE TALK - Introduction to nanoscale materials -Introduction Introduction to to nanoscale nanoscale materials materials - -Small magnetic particles -Encapsulated nanoparticles:preparation and charaterization -Bioferrofluids for local drug delivery -Summary

Nanoscale is the meeting point between the molecular chemistry and condensed matter Nanociencia Quantum Condensed Matter Physics Chemistry Top-down Botton-up Bacteria Macromolecules Mesoscopic world >100 nm 0.1 nm Virus Thin films >10 nm >0.1 nm Nanoparticles >10 nm

The macroscopic world offer materials with a determine functionality wich can be modify by size reduction Metals Metals Electrónic. Semicon- Supercon- Semicon- Supercon- ductors ductors ductors ductors Magnetic. Cataliz. Materials Materials Function Polymers Ceramics Polymers Ceramics Compo- Biomat. Coating Compo- sites sites

Applications of Nanoscience Scale reduction at nanoscopic level open new views for science and applications -Therapeutic drugs -Harder metals -Tagging of DNA and DNA chips -Catalysts -Information storage -Sensors based in nanoporous membranes -Magnetic refrigeration -Improved batteries .......

Medical application of magnetic nanoparticles Selective drug delivery Biological Hiperthermy labeling Bioferrofluid Contrast Oftalmology agent

OUTLINE OF THE TALK OUTLINE OF THE TALK -Introduction to nanoscale materials - Small magnetic particles -Small Small magnetic magnetic particles particles - -Encapsulated nanoparticles:preparation and charaterization -Bioferrofluids for local drug delivery -Summary

How small small? ? How 30 nm � 5 % atoms at the surface 10 nm � 20 % atoms at the surface 3 nm � 50 % atoms at the surface

Crítical size for single-domain particle -Under size reduction the coercive field increases and the the particle becomes single- domain -When E K =KV as V � 0 then E K � 0 superparamagnetic limit KV = k B T -At this situation the particle magnetic moment will fluctuate independently of the particle

Classic paramagnet Quantum paramagnet If K>>> If K � 0 The supermoment follows The supermoment follows the Langevin law the Brillouin J=1/2 law

Real superparamagnetic system -No hystheresis -The isotherm presents a universal H/T behaviour

Time effects:relaxation Due to the stocastic nature of the thermal energy the superparamagnetism is a time dependent effect τ = τ 0 exp(-KV/k B T) τ time for magnetization reversal (depend on the anisotropy) Si τ < τ measure superparamagnetism τ 0 tipically 10 -9 s Critical volume to detect superparamagnetism: V sp =25(k B T/K) τ measure =100 s T B =KV sp /25k B V sp =4.5(k B T/K) τ measure =10 -7 s T B =KV sp /4.5k B T B Mösbauer = 5.5 T B magnetometry (FC y ZFC) Fe y Co at 300K V sp =16 y 7.6 nm

OUTLINE OF THE TALK OUTLINE OF THE TALK -Introduction to nanoscale materials -Small magnetic particles - Encapsulated nanoparticles:preparation -Encapsulated Encapsulated nanoparticles:preparation nanoparticles:preparation - and charaterization and charaterization charaterization and -Bioferrofluids for local drug delivery -Summary

Particles coating: Carbon and Silica nanocages The discovery of graphitic nanostructures as fullerenes and nanotubes offers the possibility to fill nanoscale cavities w ith transition metals The confinenement of this small amount of material promises: -Novel physical properties -Protection of the encapsulated metals from oxidation by resistant carbon cages

Kratschmer-Huffman Method -The anode is a graphite-metal composite -Several carbon and graphitic structures are obtained Gas DEPOSIT “SOOT” ANODE CATODE “COLLARETTE” “WEB-LIKE SOOT” Refrigeration Vacuum

Arc-discharge Furnace Products showing the web- like soot on the collarette -Fullerenes -Amorphous carbon -Graphitic structures

Manganese encapsulated nano particles -Graphitic multiw all nanotubes -Catalytic particles forming large single w all nanotubes -Small particles sourronded by polygonal layers: Onions -Metallic inclusions in nanotubes -Nanoparticles encapsulated in graphitic layers and glassy carbon 25 nm

TEM images of Fe & Co encapsulated nanoparticles Co Fe

Fe coated by graphitic layers

Sample treatment an average size -Samples are sonicated in a dilution of surfactant (SDS and distilled w ater (5g/l)) -Magnetic separation is acheived in a field gradient of 3 kOe/cm -Chemical etching w ith aqua regia is made to remove the uncovered metallic particles 14 12 10 8 73 sam ples Counts 6 4 2 0 5 10 15 20 25 30 35 Size (nm)

Magnetic characterization -SQUID magnetometry -Mössbauer spectroscopy Si τ < τ medida superparamagnetism Critical volume to detect superparamagnetism: V sp =25(k B T/K) τ static =100 s T B =KV sp /25k B V sp =4.5(k B T/K) τ mössbauer =10 -7 s T B =KV sp /4.5k B

Móssbauer spectroscopy No indication of SP relaxation at room temperature Estimated particle size 13-9 nm (interparticle interaction) α− Fe Fe Tw o Tw o sextets extets (34T and 34T and 31T) 31T) Fe Fe 3 C A sextet A sextet (25.1 T) (25.1 T) γ -Fe Singlet Singlet and and doublet doublet H.R. Rechenberg et al. J. Magn. Magn. Mat 226-230 (2001) 1930

Magnetization measurements Blocked particles Superparamagnetic particles Large/correlated particles Small particles

Blocking temperature is determinaed from FC and ZFC Field cooling Fe WM114 Zero field cooling 16 Separada 14 14 12 12 10 emu/g 8 Counts 73 samples 500 Oe Sin purificar 10 6 4 8 Separada y atacada 2 0 6 5 10 15 20 25 30 35 Size (nm) 0 50 100 150 200 250 300 350 T(K)

Silica encapsulated encapsulated Fe nanoparticles Fe nanoparticles Silica 200 150 100 C M (emu/g) 50 50 40 30 20 0 10 M (emu/g) 0 -10 -20 -50 -30 -40 -50 -100 -60 -1500 -1000 -500 0 500 1000 1500 2000 H (Oe) -150 -200 -40000 -30000 -20000 -10000 0 10000 20000 30000 40000 H (Oe)

Fe encapsulated in Silica X-Ray Photoelectron Spectroscopy Photons Electrons Before etching After Fe etching

Fe encapsulated nanoparticles Electron Energy Loss Spectra (EELS) (in collaboration J. Arbiol) b) 700000 Fe L 3 edge a) 600000 e - Fe x O y 500000 A.U. e - 400000 Fe L 2 edge a Surface Spectrum Fe 300000 b Inside Spectrum 200000 O K edge 100000 0 EELS 500 550 600 650 700 750 800 Electron Energy Loss (eV) 250000 SiO 2 Si L 2,3 edge Fe Fe 200000 SiO 2 Fe A.U. 150000 Al L 2,3 edge 100000 50000 0 70 80 90 100 110 120 130 140 150 Electron Energy Loss (eV)

High Resolution Transmision Electron Microscopy of carbon encapsulated iron nanoparticles (32-2) (02-2) (300) Fe 2 O 3 Nanoparticle Graphite Encapsulation [011] Fe 2 O 3 Maghemite HRTEM EFTEM Elemental Map EFTEM EFTEM Red: K C (284 eV) K C (284 eV) L 3 Fe (708 eV) Green: L 3 Fe (708 eV)

OUTLINE OF THE TALK OUTLINE OF THE TALK -Introduction to nanoscale materials -Small magnetic particles -Encapsulated nanoparticles:preparation and charaterization - Bioferrofluids for local drug delivery -Bioferrofluids Bioferrofluids for for local drug local drug delivery delivery - -Summary

BIOFERROFLUIDS AS THERAPEUTIC CARRIERS BIOFERROFLUIDS AS THERAPEUTIC CARRIERS -They should be magnetic to by guided by applied magnetic fields -The magnetic materials are not biocompatibles - The nanoparticles should be encapsulated -The sourrounded material should be able to adsorb and desorb the drug J.Johnson et al., EC&M 3 (2002) 12

Local drug delivery by using magnetic carriers New development at the INA Solid tumor Lapararoscopic implant of a permanent magnet Magnet implantation Intravenous administration of magnetic carriers External applied magnetic field

BIOFERROFLUIDS BIOFERROFLUIDS Graphite -Biocompatibility Encapsulation -Drug adsortion/desorption -Proteins conjugation Fe 2 O 3 Nanoparticle Plasma Krästchmer-Hoffman HRTEM Fe 2 O 3 Maghemite C Graphite

Endoscope Trocar for magnet implantation Implant In-Vivo localization of magnetic particles by systemic administration and using magnetic implants Bioferrofluid Intravenous administration In coll. Hospital Clínico Veterinario

Magnet implant in the left kidney Localization of nanoparticles Right kydney witout magnetic implant Lack of nanoparticles

Kidney with with magnetic magnetic implant implant: : Kidney Moderate concentration concentration of nanoparticles of nanoparticles Moderate Rabbit 22 Rabbit 23

Nanoparticles Nanoparticles traveling in in blood blood traveling Tested biocompatibility