Engineering Nanoparticles for Biomedical Applications Mamoun Muhammed, Prof Chairman, Functional Materials Department Chairman, Functional Materials Department Royal Institute of Technology (KTH), Stockholm Royal Institute of Technology (KTH), Stockholm London, September 2-3, 2010 1 st International Workshop on Nanomedicines
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Engineering Nanoparticles for Biomedical Applications
Mamoun Muhammed, Prof
Chairman, Functional Materials DepartmentChairman, Functional Materials Department
Royal Institute of Technology (KTH), StockholmRoyal Institute of Technology (KTH), Stockholm
London, September 2-3, 2010
1st International Workshop on Nanomedicines
Engineering Nanoparticles for Biomedical Applications
1.Magnetic Nanoparticles• SPION for MRI• Thermally blocked NP for biodiagnostics
2.Nanoparticles for Drug Delivery• Multifunctional NP• Thermosensetive NP
3.Ferrogel for drug delivery
2010-09-06 IM2655 Intro to nanotech 3
FDA calls it "nanotechnology" only if it involves all of the following:
1.Research and technology development, or products regulated by FDA, that are at the atomic, molecular or macromolecular levels, and where at least one dimension, that affects the functional behavior of the product, is in the length scale range of approximately 1-100 nanometers. (Man-made materials)
2. Creating and using structures, devices and systems that have novel properties and functions because of their small and/or intermediate size.
3. Ability to control or manipulate at the atomic scale.
Definition
Dendrimers
Magnetic NanoparticlesLiposomes
Polymernanoparticles
Medical applicaltions of nanoparticles
• Magnetic resonance
imaging
enhancement
• Single cell study and bio‐
manipulation
• Novel diagnostic tools for
early stage detection of
diseases
• Fast and more efficient
biosensors
• Targeted drug delivery to
specific cells
• Novel cancer theraphy
and hyperthermia
treatments
Nature Nanotechnology, 2007, 2, 469-478 4
Nanoparticle Engineering
Reactant gas molecules
Chemical Reaction Chemical Reaction&Coagulation(coalescence)
• Templates Precipitation in microemulsion• Precipitation in presence of surfactants
• Others Sono-chemical reactions
Superparamagnetic and Thermally blocked nanoparticles with strong magnetic response
Design of tailored Magnetic Nanoparticles
•
Magnetite (Fe3
O4
)•
Maghemite (γFe2
O3
)•
Ferrites (CoFe2
O4, ZnFe2
O4, MnFe2
O4
, …) •
Iron Platinum (FePt) & CoPt
Bio-compatibility and surface functionalisation
•
Inorganic: Gold, Silica, hydroxyappatite, ...•
Organic: Dextran, PVA, PEG, mPEG, …
A)
B)
2 3 4 5 6 7 8 90
10
20
30
40
50
60
<D> = 5.7 nm
Freq
uenc
y (%
)
Diameter (nm)
6 8 10 12 14 16 180
5
10
15
20
25
<D> = 12nm
Freq
uenc
y (%
)
Diameter (nm)
TEM images (left) and the corresponding particle size histograms (right) of magnetite nanoparticles prepared by controlled coprecipitation. (A) without heat treatment and (B) after heat treatment (80ºC for 1hrs)
Magnetite
Magnetic characterisation
VSM measurement for SiO2 coated Fe3 O4
by co-precipitation
Superparamagnetic iron oxide nanoparticles
• Average particle size=12 nm•
XAS shows nonstochiometric phase Fe3
O4-δ
, the curve shifts to Fe2+.
After one year shelf storage
Magnetic Nanoparticles•
Oxide : magnetite, ferrite •
Metal : Fe, Co, PtFe, CoPt
Coating
Surface Functionalization of Magnetic Nanoparticles
Thermally Blocked NanoparticlesMagnetic Relaxation for Bio-Diagnostics
Detect specific biomolecules by measuring changes in Brownian relaxation of thermally blocked magnetic nanoparticles.
Biosensor Based on Magnetic Relaxation
Kindly provided by IMEGO Institute (Göteborg - Sweden)Fornara, A. et al, NanoLetters (2008)
shift in the maximum of the imaginary magnetic susceptibility.
Brownian relaxation process can be detected in the frequency domain
M = magnetisationH = alternating
externalmagnetic
fieldχ = complex magnetic
susceptibility
H)i(HM ''' χχχ −==
Bio-diagnostics based on Magnetic Relaxation
IMEGO AB
Synthesis of Thermally blocked Magnetic nanoparticles
Quantitative detection of PSA byBrownian relaxation frequency measurements
1000100
• No pretreatment
• Simple mixing of fluids
• Fast
• Multiple bio molecules detection
• Practical for point of use
AC susceptometer
Magnetic nanoparticles + LPS + serum sample
Magnetic nanoparticles added to LPS
Serum sample
0 20 40 60 80 100
260
280
300
320
340
360
380
Serum Control
Med
ian
diam
eter
[nm
]
Amount of positive serum %
0.00 0.05 0.10 0.15 0.20
280
300
320
340
360
380
400
mAb PSA66M
edia
n di
amet
er [n
m]
mAb [mg/mL]
Fornara, A. et al, NanoLetters (2008)
Detection of Brucella
Antibodies in Serum
Detection limit: 0.05 µg/ml
Nanomaterials in Biology and Medicine
Targeted drug delivery – Targeted drug delivery using a multicomponent nanoparticle containing therapeutic as well as biological surface modifying agents
Biocompatible Polymers
* O *
O
Poly ¥å-caprolactone
*O
*
O
Poly lactide
*O
*
O
Poly glycolide
*NH
*
O
CH2
CH2
CH2
CH2
NH2
Poly L-lysine
* CH2 *
N
O
O
Poly(ethyl-2-cyanoacrylate)
Amphiphilic copolymer for biodegradable nanosphere
Jo. Y. S,et al, Nanotechnology 2004, 15 (9),1186-1194.
Self-assembly of gold nanoparticles on the surface of PLA-mPEG nanospheres
Silanization
Gold nanoparticle self-assembly
Y. S. Jo, M. Muhammed, et al., J. Materials Science: Materials in Medicine 2005
TEM images of ‘shell-in-shell’ structure nanoparticles
a) PLLA-PEG micelleb) ‘shell-in-shell’ structures covered with Au nanoparticles in partc) - d) ‘shell-in-shell’ structures fully covered with Au nanoparticles Y. S. Jo, J Mat Sci.; Mat in Medicine
(2004)
Drug Release Profile Dissolution regime
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 5 10 15 20
Time [hrs]
c1∞
Vr/
c0
Diffusion modelDissolution modelDL1
Drug Release Profile Dissolution- Diffusion Regimes