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

▶
biomedical applications based on biomedical applications
SMART_READER_LITE
LIVE PREVIEW

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

Oct 26, 2023 462 likes •867 views

Biomedical applications based on Biomedical applications based on magnetic nanoparticles magnetic nanoparticles R. Fernndez-Pacheco 1 , C. Marquina 2 , D. Serrate 2 and J.G Valdivia 1 M. Gutierrez 1 and M.R. Ibarra 1,2 1 Instituto

slide-1
SLIDE 1

“ “Biomedical applications based on Biomedical applications based on magnetic nanoparticles magnetic nanoparticles” ”

  • R. Fernández-Pacheco1, C. Marquina2 , D. Serrate2 and J.G Valdivia1
  • M. Gutierrez1 and M.R. Ibarra1,2

1Instituto de Nanociencia de Aragón, Edificio Interfacultades II, Zaragoza

(Spain)

2Instituto de Ciencia de Materiales de Aragón (CSIC/Universidad de

Zaragoza), Facultad de Ciencias, Zaragoza (Spain Constanta 2005

slide-2
SLIDE 2

OUTLINE OF THE TALK OUTLINE OF THE TALK

  • Introduction

Introduction Introduction to to to nanoscale nanoscale nanoscale materials materials materials

  • Small magnetic particles
  • Encapsulated nanoparticles:preparation

and charaterization

  • Bioferrofluids for local drug delivery
  • Summary
slide-3
SLIDE 3

Nanoscale is the meeting point between the molecular chemistry and condensed matter

Quantum Chemistry Bacteria >100 nm Virus >10 nm Nanoparticles >10 nm Thin films >0.1 nm Macromolecules 0.1 nm Condensed Matter Physics Nanociencia Mesoscopic world Botton-up Top-down

slide-4
SLIDE 4

The macroscopic world offer materials with a determine functionality wich can be modify by size reduction

Semicon- ductors Semicon- ductors Polymers Polymers Compo- sites Compo- sites

Ceramics Ceramics

Supercon- ductors Supercon- ductors Metals Metals

Materials Materials

Magnetic. Biomat. Coating Cataliz. Electrónic. Function

slide-5
SLIDE 5

Applications of Nanoscience

Scale reduction at nanoscopic level open new views for science and applications

  • Therapeutic drugs
  • Tagging of DNA and DNA chips
  • Information storage
  • Magnetic refrigeration
  • Harder metals
  • Catalysts
  • Sensors based in nanoporous

membranes

  • Improved batteries .......
slide-6
SLIDE 6

Medical application of magnetic nanoparticles

Biological labeling Contrast agent Oftalmology Hiperthermy Selective drug delivery Bioferrofluid

slide-7
SLIDE 7

OUTLINE OF THE TALK OUTLINE OF THE TALK

  • Introduction to nanoscale materials
  • Small

Small Small magnetic magnetic magnetic particles particles particles

  • Encapsulated nanoparticles:preparation

and charaterization

  • Bioferrofluids for local drug delivery
  • Summary
slide-8
SLIDE 8

30 nm 5 % atoms at the surface 10 nm 20 % atoms at the surface 3 nm 50 % atoms at the surface

How How small small? ?

slide-9
SLIDE 9

Crítical size for single-domain particle

  • Under size reduction the coercive field increases and the the particle becomes single-

domain

  • When EK=KV as V 0 then EK 0 superparamagnetic limit
  • At this situation the particle magnetic moment will fluctuate independently of the particle

KV = kBT

slide-10
SLIDE 10

Classic paramagnet Quantum paramagnet

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

slide-11
SLIDE 11

Real superparamagnetic system

  • No hystheresis
  • The isotherm presents a universal H/T behaviour
slide-12
SLIDE 12

Time effects:relaxation

Due to the stocastic nature of the thermal energy the superparamagnetism is a time dependent effect

τ = τ0 exp(-KV/kBT) τ time for magnetization reversal (depend on

the anisotropy) Si τ <τmeasure superparamagnetism

τ0 tipically 10-9 s

Critical volume to detect superparamagnetism: Vsp=25(kBT/K) τmeasure =100 s TB=KVsp/25kB Vsp=4.5(kBT/K) τmeasure =10-7s TB=KVsp/4.5kB TB Mösbauer = 5.5 TB magnetometry (FC y ZFC) Fe y Co at 300K Vsp=16 y 7.6 nm

slide-13
SLIDE 13

OUTLINE OF THE TALK OUTLINE OF THE TALK

  • Introduction to nanoscale materials
  • Small magnetic particles
  • Encapsulated

Encapsulated Encapsulated nanoparticles:preparation nanoparticles:preparation nanoparticles:preparation and and and charaterization charaterization charaterization

  • Bioferrofluids for local drug delivery
  • Summary
slide-14
SLIDE 14

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

slide-15
SLIDE 15

Kratschmer-Huffman Method

  • The anode is a graphite-metal composite
  • Several carbon and graphitic structures are obtained

CATODE

Refrigeration Gas Vacuum

ANODE “SOOT” DEPOSIT “WEB-LIKE SOOT” “COLLARETTE”

slide-16
SLIDE 16

Arc-discharge Furnace

Products showing the web- like soot on the collarette

  • Fullerenes
  • Amorphous carbon
  • Graphitic structures
slide-17
SLIDE 17

Manganese encapsulated nano particles

25 nm

  • 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

slide-18
SLIDE 18

TEM images of Fe & Co encapsulated nanoparticles

Fe Co

slide-19
SLIDE 19

Fe coated by graphitic layers

slide-20
SLIDE 20

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

5 10 15 20 25 30 35 2 4 6 8 10 12 14 Counts Size (nm) 73 sam ples

slide-21
SLIDE 21

Magnetic characterization

  • SQUID magnetometry
  • Mössbauer spectroscopy

Si τ <τmedida superparamagnetism Critical volume to detect superparamagnetism: Vsp=25(kBT/K) τstatic=100 s TB=KVsp/25kB Vsp=4.5(kBT/K) τmössbauer =10-7s TB=KVsp/4.5kB

slide-22
SLIDE 22

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 3C

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

slide-23
SLIDE 23

Magnetization measurements

Blocked particles Large/correlated particles Superparamagnetic particles Small particles

slide-24
SLIDE 24

Blocking temperature is determinaed from FC and ZFC

5 10 15 20 25 30 35 2 4 6 8 10 12 14 Counts Size (nm) 73 samples

50 100 150 200 250 300 350 6 8 10 12 14 16

Field cooling Zero field cooling

emu/g T(K) Sin purificar Separada Separada y atacada Fe WM114

500 Oe

slide-25
SLIDE 25
  • 40000
  • 30000
  • 20000
  • 10000

10000 20000 30000 40000

  • 200
  • 150
  • 100
  • 50

50 100 150 200

M (emu/g) H (Oe)

  • 1500
  • 1000
  • 500

500 1000 1500 2000

  • 60
  • 50
  • 40
  • 30
  • 20
  • 10

10 20 30 40 50

M (emu/g) H (Oe) C

Silica Silica encapsulated encapsulated Fe nanoparticles Fe nanoparticles

slide-26
SLIDE 26

Fe encapsulated in Silica X-Ray Photoelectron Spectroscopy Fe

Photons Electrons After etching Before etching

slide-27
SLIDE 27

Fe encapsulated nanoparticles Electron Energy Loss Spectra (EELS) (in collaboration J. Arbiol)

e- e- a) b) FexOy Fe EELS

aSurface Spectrum bInside Spectrum

500 550 600 650 700 750 800 100000 200000 300000 400000 500000 600000 700000

A.U.

Electron Energy Loss (eV)

O K edge Fe L3 edge Fe L2 edge

Fe SiO2 Fe Fe SiO2

70 80 90 100 110 120 130 140 150 50000 100000 150000 200000 250000

Electron Energy Loss (eV)

A.U. Si L2,3 edge Al L2,3 edge

slide-28
SLIDE 28

High Resolution Transmision Electron Microscopy of carbon encapsulated iron nanoparticles

Fe2O3 Nanoparticle Graphite Encapsulation

HRTEM

(32-2) (300) [011] Fe2O3 Maghemite (02-2)

EFTEM

K C (284 eV)

EFTEM

L3 Fe (708 eV) EFTEM Elemental Map

Red: K C (284 eV) Green: L3 Fe (708 eV)

slide-29
SLIDE 29

OUTLINE OF THE TALK OUTLINE OF THE TALK

  • Introduction to nanoscale materials
  • Small magnetic particles
  • Encapsulated nanoparticles:preparation

and charaterization

  • Bioferrofluids

Bioferrofluids Bioferrofluids for for for local drug local drug local drug delivery delivery delivery

  • Summary
slide-30
SLIDE 30

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

slide-31
SLIDE 31

Local drug delivery by using magnetic carriers

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

slide-32
SLIDE 32

BIOFERROFLUIDS BIOFERROFLUIDS

Fe2O3 Nanoparticle Graphite Encapsulation Fe2O3 Maghemite

HRTEM

C Graphite

Plasma Krästchmer-Hoffman

  • Biocompatibility
  • Drug adsortion/desorption
  • Proteins conjugation
slide-33
SLIDE 33

Endoscope Trocar for magnet implantation Implant

In-Vivo localization

  • f magnetic

particles by systemic administration and using magnetic implants

Bioferrofluid Intravenous administration In coll. Hospital Clínico Veterinario

slide-34
SLIDE 34

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

slide-35
SLIDE 35

Kidney Kidney with with magnetic magnetic implant implant: : Moderate Moderate concentration concentration of nanoparticles

  • f nanoparticles

Rabbit 22 Rabbit 23

slide-36
SLIDE 36

Nanoparticles Nanoparticles traveling traveling in in blood blood

Tested biocompatibility

slide-37
SLIDE 37

Dynamic Dynamic of

  • f the

the adsorption adsorption and and release release of

  • f Doxorubicine

Doxorubicine on

  • n carbon

carbon coated coated magnetic magnetic nanoparticles nanoparticles

20 40 60 80 100 120 140 160 180 0.00 0.05 0.10 0.15 0.20 0.25 0.30

C desorbida DOX (mg/ml) t (h) C Polynomial Fit of Dat

  • 20

20 40 60 80 100 120 140 160 180 200 2 4 6 8

Data Fit t (min) C doxorrubicina adsorbida (µg/ml)

Adsorption Desorption Saturation after 20 minutes Complete release after 100 hours

slide-38
SLIDE 38

Matter manipulation at atomic level I nteligent nanovectors Targeting

slide-39
SLIDE 39
slide-40
SLIDE 40