Design of Polymeric Nanostructures for
Chemical and Biomedical Applications
Michael KC Tam
Department of Chemical Engineering
20
0
8
University of Waterloo
200 University Avenue West
Waterloo, Ontario, CANADA N2L 3G1
R
UW Quantum
Quantum--Nano Centre
IP
Revolutionary Technology Waves
1
The Size of Things
1-5 nm
20-50 nm
8
Via selfself-assembly
20
0
Human hair
Via polymerization (varying MWs)
R
Macromolecules (Polymers)
IP
Visionary in Polymer Science!
‘‘In the meantime, macromolecular chemistry, too, has
become a classical discipline, a mature science, with all the advantages
and handicaps of maturity. Harvest is plentiful, the results are abundant –
but one has to ask: where is the future, where are the adventures?’’
Quote by Helmut Ringsdorf
H. Ringsdorf, B. Schlarb, J. Venzmer, Angew.
Angew. Chem. Int. Ed. Engl. 1988, 27,
27, 113.
Dr. Ringsdorf promotes cross
cross--disciplinary discussions and collaborations in the field of
polymer chemistry, biology
biology,, physics and medicine
2
Self-assembly in Nature: (1) DNA
8
Source: http://www.paternityexperts.com/img/DNA-of-life.jpg
Slide 5 of 88
R
20
0
Length of a DNA = 20,000 μm (or 2 m)
Length of a chromosome = 2 μm
IP
Self-assembly in Nature: (2)
Protein
hemoglobin
http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2005/Heiner/hemogl
obin_ribbon_4subunits.jpg
α-hemolysin
3
R
20
0
8
Self-assembly in Nature: (3) Microtubuli
IP
Self-assembly in Nature: (4) Viral capsids
http://www.sb.fsu.edu/~caspar/graphics/tmv3.gif
4
8
20
0
R
Self-assemb
bly in Nature
e: (5) Lipids
and Biomembra
anes
http://upload.wikimedia.org/wikipedia/commons/e/ee/CellMembraneDrawing.jpg
Polymers and Copolymers
IP
Polymer science, having an old tradition as an interdisciplinary field, can no longer restrict
itself to common plastics. Attempts to reach new horizons have already begun.
• Dendrimers
• Others ………..
5
RESEARCH INTERESTS
SCIENTIFIC TOOLS
Light scattering
Titration calorimetry
Spectroscopy(UV,
Spectroscopy(UV FTIR)
Microscopy--TEM, SEM
Microscopy
Rheometry
Physics & Thermodynamics
Polymer-surfactant interactions
PolymerDrug--polymer interactions
Drug
Self--assembly behavior
Self
20
0
APPLICATIONS
Drug delivery
Nano--templates
Nano
Coatings & Personal care
R
COLLABORATORS
Dow Chemicals
Singapore--MIT Alliance
Singapore
Bioprocessing Tech Inst.
8
Colloids
&
Polymers
IP
RESEARCH STRATEGY & PLAN
Monomers
A and B
N
Fullerene
Starting materials
In water
ATRP/EP
Synthetic Methods
+
Hydrophobic
drugs
micelle
Block copolymers, nanoogels
& water-soluble fullerenes
nucleus
target cell
Delivery of drugs to targeted sites
Microstructure & thermodynamics
6
Plasmid DNA
+
Various Delivery Systems
Block
copolymer
target
cell
endocytosis
Genes/DNA
Simplex micelle
Protein
based
Drugs
+
Protein drugs
Block
copolymer
Hydrophobic
Drugs
target
cell
endocytosis
Simplex micelle
8
Hydrophobic drugs
nucleus
+
target cell
R
20
0
micelle
IP
POLYMERIC DRUG DELIVERY
SYSTEMS
Sinaga, A., Hatton, T.A., Tam,
K C Macromolecules (2007)
K.C.,
(2007),
40, 9064-9073
Sinaga, A., Hatton, T.A., Tam,
K.C., Biomacromolecules (2007)
8, 2801-2808.
Sinaga, A., Ravi, P., Hatton, T.A.,
Tam, K.C., Journal of Polymer
Science Part A: Polymer
Chemistry (2007), 45 (13), 26462656
Peptide
p
based block
copolymers
Modified Pluronic
block copolymers
• Tian, Y., Bromberg, L., S.N.
Lin, Hatton, T.A., Tam,
K.C., Journal of Controlled
Fullerene block
Release (2007), 121 (3),
•
Tan,
B.H.,
Ravi,
P.,
Tan,
137-145.
copolymers
L.N., Tam, K.C., Journal • Tian, Y., Ravi, P.,
• Wang C., Ravi, P., Tam, of Colloid & Interfacial
Bromberg, L., Hatton, T.A.,
K.C., Langmuir (2007), Science (2007), 309 (2), Tam,
Tam K
K.C.,
C Langmuir
23, 8798-8805.
453-463).
(2007) 23,
• Ravi, P., Dai, S., Wang, • 2638-2646.Tan, J.P.K., • Xiong, X.Y., Li, Y., Li, Z.,
C., Tam, K.C., Journal
Tam, K.C., Journal of
Zhou, C., Tam, K.C., Liu,
of Nanoscience and
Controlled Release
Z., Xie, G., Journal of
Nanotechnology (2007), (2007), 118, 87-94.
Controlled Release (2007),
7 (4-5), 1176-1196.
• Tan, B.H., Ravi, P., Tam, 120, 11-17.
• Wang, C., Ravi, P., Dai, K.C., Macromolecular
S., Tam, K.C., Langmuir Rapid Communications
(2006), 22 (17), 7167(2006), 27,522-528.
7174.
Microgel and
nanogel systems
7
CH3
CH3
O
O
OH
O
n
N
m
pH responsive reverse micelle
CH3
CH3
C
CH3
Br
O
O [CuCl]:[HMTETA]/Methanol
Hydrolysis
O
+
O
C
CH3
CH3
CH2
CH2
O
O
O
OH
CH3
CH3
CH3
CH2
n
N
n
CH3
N
CH3
CH3
CH3 m
P(MAA-b-DMAEMA)
Low pH
DMA
block
MAA
block
8
Hydrophobic
High pH
Hydrophilic
20
0
P(MAA-b-DMAEMA)
R
Mao, B.W., Gan, L.H., Gan, Y.Y., Tam, K.C., Tan, O.K., Polymer (2005), 46, 10045-10055.
Dai, S., Ravi P., Tam, K.C., Mao B.W., Gan
L.H.,Langmuir (2003), 19, 5175-5177
IP
Micellization Behavior of P(DEA-b-MAA)
(a)
C
H2C
C
pH = 12
p
C O
C O
OH
(b)
e
CH3
e
CH3
CH2
O
n
d CH2
pH = 12
b
H2C
c CH2
b
N CH2
CH3
a
CH3 m
a
pH > 9.2
no
a
f(Rh)
no
b & c
DEA core with
MAA shell
a
pH = 7
pH = 3
b
pH = 3
c
d
5
4
pH < 5.5
e
3
2
1
δ (ppm )
0
0.1
10
Rh (nm )
1000
MAA core with
DEA shell
8
α-Cyclodextrin Induced Assembly
of PEO-b-PAA at high pH
α-CD
PEO-b-PAA
165 nm
51nm
R
20
0
Double
Double--hydrophilic
poly(ethylene
oxide)oxide)-bpoly(acrylic acid) (PEO(PEO-b-PAA) self
self--assembled
into nanostructures in basic solution upon the
addition of α-cyclodextrin (α(α-CD).
CD). SelfSelf-assembly
was induced by the complexation between α-CD
and PEO segments
segments..
8
Aggregation
Number ~4130
IP
Plasmid DNA interaction with
PDEA-b-PEO-Biotin
+
+
PDEA
+
Biotin
PEO
+
Biotin
Plasmid DNA
37 kB
PDEA70-b-PEO113Mn=18,000 Da, PDI = 1.3
30
CH3O-PEO-OH
PEO-b-PDEAEMA
ζ Potential (mV))
B-PEO-b-PDEAEMA &
starting PEO
N/P= Ratio of DNA over Polymer
20
HO-PEO-OH
B-PEO-b-PDEAEMA
10
0
-10
-20
-30
PEO-b-PDEAEMA &
starting PEO
4
5
0
1
2
3
4
5
6
7
N/P ratio
6
7
retention time (mins)
8
Tan, J.F., Ravi, P.;Too, H.P., Hatton, T.A., Tam, K.C.*,
Biomacromolecules (2005), 6, 498-506
9
Plasmid DNA
interaction with
PDEA-b-PEO-Biotin
+ +
+
PDEA
PEO
+
Biotin
N/P ratio
0.1
1
10
100
region where
polymer unimers
coexist with
Polymer/DNA
complexes
90
+
+
+
+
+
++
+
70
+
60
+
++
+
1
2
30
0.001
0.01
Region 1: +ve PDEA decorating on
DNA molecules
Blue region: loose aggregates
comprising of PDEA and DNA
Region
2:
at
high
PDEA
concentration or large N/P ratio,
simplex micelles are produced.
8
+
50
40
+
+
+
20
0
Rh (nm)
80
+
100
0.1
1
In--vitro studies are now underway
In
R
PEO-b -PDEAEMA conc. (mg/ml)
IP
Delivery of Various Payloads (e.g. drugs,
chemicals) using Coated Microgels
Journal of Controlled Release (2008)
10
R
20
0
8
Release Kinetic from Coated Microgels
IP
Mechanism Controlling Drug Delivery
from Coated Microgels
Bare MAA-EA
nanogel
3 coated layer
nanogel
PrHy
PAH
Cross-linked junction
PSS
4 coated layer
nanogel
11
Fullerene System (Bucky Ball)
Drawbacks
Solutions
9
Solubility
¾
Graft small molecules
9
Processability
¾
Graft polymers
9
Applications Hindered
¾
Charge transfer complexes
Grafting small groups
R
R
Grafting of Polymers
CT Complex
N
n
N
N
N
20
0
Well-defined grafting
8
R
R
Amphiphilic behaviour
IP
pH-responsive Fullerene
System
Polymethacrylic acid-b-C60
z
z
z
PMAA125-b-C60
Mn~10,800 Da
Mw/Mn= 1.18
CH3
CH2 C
nn
C=O
O
OH
Ravi, P., Dai, S., Tan, C.H., Tam, K.C. Macromolecules (2005), 38, 933-939.
Yu, H., Gan, L. H., Hu, X., Venkatraman, S. S., Tam, K. C., Gan, Y. Y.,
Macromolecules (2005), 38, 9889-9893
Teoh, S.K., Ravi, P., Dai, S., Tam, K.C., Journal of Physical Chemistry B (2005),
109, 4431-4438.
Ravi, P., Dai, S., Tam, K.C., Journal of Physical Chemistry B (In Press).
C(CH3)3
12
Nano-particles and
nano-fractals
Nano-fractals
Of NaCl crystals
Dense Nano-fractals
Of NaCl crystals
Nano-particles
(100-200 nm)
NaCl crystals on
Nano-particles
Dense NaCl crystals
on Nano-particles
8
0
Nano-particles
(200-400 nm)
0.0 M NaCl
20
0
Neutrralisation Degree
1
0.2M NaCl
AFM`
R
Tan, C.H., Dai, S., Ravi, P., Tam, K.C., Langmuir (2004), 20, 9901-9904
0.5M NaCl
IP
Naturally occurring fractal patterns
13
INTERACTION WITH NONIONIC SURFACTANTS
0
X100 to H2O
X100 tto PAA a=0
0
X100 to PAA a=1
X100 to PAA-C60 a=0
X100 to PAA-C60 a=1
-1
1
-2
ΔH kJ/mol
-3
-4
-5
-6
-8
C8H17
-9
O CH2CH2O
20
0
-10
8
-7
0.1
CTX100 (mM)
1
H
10
R
0.01
n
IP
INTERACTION WITH NONIONIC SURFACTANTS
800
(b)
700
( )
(a)
(b)
C60-b-PAA
Rh
app
(nm)
600
500
400
(c)
300
(a)
200
(d)
percipitation region
100
0
0
C8H17
0.5
1
1.5
CTX100 (mM)
O CH2CH2O
2
n
2.5
(c)
(d)
H
14
INTERACTION WITH NONIONIC SURFACTANTS
800
C60-b-PAA
700
(1)
Rh
app
(nm)
600
(1)
(2)
(3)
500
400
C60-b-PAAPAA-b-C60
300
200
100
(4)
(1) (2)
0
0
1
2
3
4
5
(3)
(4)
O CH2CH2O
n
H
R
20
0
C8H17
8
C TX100 (mM)
IP
RECENT RESEARCH ACTIVITIES
in NANOTECHNOLOGY
Protein purification
MRI Imaging
g g contrast agents
g
Removal of contaminants
Collaborators:
Prof. Alan Hatton, MIT
Prof. Miranda Yap, BTI
Nano-templating Systems
Tissue engineering
Novel catalysts
Collaborators:
Prof. Schilen, Lund Univ, Sweden
Prof. Yao Jia, Zeijiang Univ, China
pH-responsive microgels
pHZwiterionic microgels
Drug delivery applications
Collaborators:
Tan CB, Dow Chemicals, S’pore
Drug-polymer interactions
DrugDelivery of cancer drugs
Development of drug
electrodes
Collaborators:
Prof. Wyn-Jones, Salford, UK
15
Self--Assembly Systems for Drug and
Self
Gene Delivery Applications
WaterWater-soluble StimuliStimuli-responsive
Fullerene Systems
Dai, S., Ravi, P., Tam, K.C., Soft Matter (2008), 4, 435
Sinaga, A., Hatton, T.A., Tam, K.C., Macromolecules (2007),
40, 9064.
Tian, Y., Bromberg, L., S.N. Lin, Hatton, T.A., Tam, K.C., J.
Controlled Release (2007), 121, 137.
Liu, J.H., Sondjaja, R., Tam, K.C., Langmuir (2007), 23, 5106.
Tan, J.P.K., Tam, K.C., J. Controlled Release (2007), 118, 87.
Tan, J.F., Too, H.P., Hatton, T.A., Tam, K.C., Langmuir (2006),
22, 3744.
Ravi, P., Dai, S., Wang, C., Tam, K.C., J. Nanoscience &
Nanotechnology (2007), 7, 1176.
Ravi, P., Wang, C., Dai, S., Tam, K.C., Langmuir (2006), 22,
7167.
Ravi, P., Dai, S., Tam, K.C., J. Physical Chemistry B
(2005),109, 22791.
Ravi, P., Dai, S., Tan, C.H., Tam, K.C, Macromolecules
(2005), 38, 933.
Responsive and Smart
Microgel/Nanogel Systems
Microgel/
Polymer--Surfactant/Drug Interactions
Polymer
8
Tan, B.H., Tam, K.C., Adv. Colloid and Interface Science (2008).
Tan, J.P.K., Goh, C.H., Tam, K.C., European J. Pharmaceutical
Science, (2007), 32, 340.
Tan, B.H., Tam, K.C., Polymer (2007), 48, 6589.
Tan, B.H., Ravi, P., Tan, L.N., Tam, K.C., J. Colloid & Interfacial
Science (2007), 309, 453..
Tan, B.H., Ravi, P., Tam, K.C., Macromolecular Rapid
Communications (2006), 27,522.
R
20
0
Wang C., Ravi, P., Tam, K.C., Langmuir (2007), 23, 8798.
Wang, C., Wyn-Jones E., Sidhu, J., Tam, K.C., Langmuir
(2007), 23, 1635.
Liao, D.S., Dai, S., Tam, K.C., J. Physical Chemistry B
(2007), 111, 371.
Tam, K.C., Wyn-Jones, E, Chemical Society Reviews
(2006), 35, 693.
Wang C., Ravi, P., Tam, K.C., Langmuir (2006), 22, 2927.
IP
Former Group Members
Taman Negara
July 2004
Phuket
March 2005
16
Thank you for your attention
IP
R
20
0
animation
8
I will be happy to answer any questions you may have!
have!
Website: http://chemeng.uwaterloo.ca/mtam/
17