tayloring functions in microcapsules: responsiveness and
TRANSCRIPT
![Page 1: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/1.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery in living systemsIntracellular sensing
Conclusions and Perspectives
��� � �� �� � � � ���� � �� �� � � � ���� � �� �� � � � ���� � �� �� � � � �Department of Materials, Queen Mary University of London, UK
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 2: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/2.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery in living systemsIntracellular sensing
Conclusions and Perspectives
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 3: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/3.jpg)
Hollow Capsule Fabrication
Hollow PolyelectrolyteCapsule
Organic and inorganic colloidal particles, Dye or drug nanocrystals, emulsion droplets
Gas bubbles, biological cells, protein aggregatesSize 50nm – 50 µm.
Cores
Core removal (decomposition)
Sukhorukov, et al (1998) Colloids and Surfaces A 137, 253.Donath, et al (1998):. Angew. Chemie 37 (16), 2202
![Page 4: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/4.jpg)
Layer-by-layer Capsules
�� Size and shape are determined by Size and shape are determined by templating colloid particle.templating colloid particle.
�� Layer constituents: Layer constituents: �������� synthetic polyelectrolytes and biopolymerssynthetic polyelectrolytes and biopolymers�������� inorganic nanoparticlesinorganic nanoparticles
�� The Capsule Wall is tunable in The Capsule Wall is tunable in NanometerNanometer range range Thickness, composition and functionality are Thickness, composition and functionality are controlled by constituents and the layer numbercontrolled by constituents and the layer number
�� 1 layer of polyelectrolyte 1 layer of polyelectrolyte �� 11--2 nm2 nm
• Encapsulation ���� micro- and nanoreactor engineering• Controlling permeability for wide class of molecules
![Page 5: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/5.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery in living systemsIntracellular sensing
Conclusions and Perspectives
External stimulus(ions, pH, temperature,
…)
Sharp physical or chemical modifications
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 6: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/6.jpg)
Temperature induced capsule shrinkahe
Capsule diameter depends on incubation temperature
10 µm
B
10 µm
CA
10 µm
AB
C
10 20 30 40 50 60 70 80 90 100
1,5
2,0
2,5
3,0
3,5
4,0
4,5
C
apsu
le d
iam
eter
/ µm
Incubation temperature / °C
CLSM
PSS
SO3
n
Na
PDADMAC
N
n
Cl
Dr. Karen Köhler
![Page 7: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/7.jpg)
Morphology of (PDADMAC/PSS)4 capsules
4,6 4,4 3,0 2,8 2,6 2,4 2,2 2,0 1,8 1,6 1,4 1,2
Capsule diameter / µm
1 µm
1 µm
1 µm 1 µm 1 µm
1 µm 1 µm 1 µm
SEM
1 µm
TEM
Temperature induced transition from a hollow shell to a full sphere
1 µm
![Page 8: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/8.jpg)
pH-sensitive hollow capsules
Sodium Poly (Styrene Sulfonate)
n
SO3- , Na+
PSS PAH
m
NH3+, Cl-
Poly (Allylamine Hydrochloride)
NaOH 0.1 M
pH
HCl 0.1 M
pH
SHRUNK STATE
(8 µµµµm)
10 µµµµm
SWOLLEN STATE(18 µµµµm)
10 µµµµm
Christophe Dejugnat
![Page 9: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/9.jpg)
Confocal fluorescence Laser Scanning
Microscopy10 µm
∆T, pH
10 µm
Impermeable„Closed gate“
10 µm
10 µm
Encapsulation and release
ReleaseEncapsulated
Permeable „Open gate“
pH, salt
![Page 10: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/10.jpg)
PAH
PVP
Tuning of electrostatic interactions by pH
��
� ��
�
Poly(allylamine hydrochloride)
Poly(4-vinylpyridine hydrochloride)
PAA
PMA
OHO
m
OHO
p
CH 3
�
�� � �
�
Poly(acrylic acid)
Poly(methacrylic acid)
Increasing hydrophobicity
NH3+
n
Cl-
N
o
H+Cl-
Weak polyelectrolytes
![Page 11: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/11.jpg)
(PAH/PMA)5 capsules templated on SiO2
• thin shells
• d2L = (3 ± 0.2) nm
• smooth surface
NH3+
n
Cl-OH
O
p
CH 3
PAH PMA
Tatjana Mauser
![Page 12: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/12.jpg)
1 2 3 4 5 6 7 8 9 10 11 123.0
3.5
4.0
4.5
5.0
5.5
6.0
caps
ule
diam
eter
, µm
pH
Influence of pH on (PAH/PMA)5 capsules
capsuledissolution
capsuledissolution
addition of HCl: pH < 2
t ~ 1 secswelling
t ~ 2 secdissolution
5 µm
5 µm
5 µm
Tatjana Mauser
![Page 13: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/13.jpg)
Optically driven Encapsulation
Matthieu Bedard – Optically addressable microcapsules
![Page 14: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/14.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery in living systemsIntracellular sensing
Conclusions and Perspectives
Remote
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 15: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/15.jpg)
TEM image
Magnetic NPs in shell
Targeted capsule delivery via magnetic field to tissues
Magnetite nanoparticles assembled in capsule wall
![Page 16: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/16.jpg)
Capsules with Composite Shell are Susceptible to Remote Activation
Ag-nanoparticles doped capsules can be ruptured by Infrared Laser 830nm
� Optically activated release; � Infrared window for biomedical application
Andre Skirtach
![Page 17: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/17.jpg)
Fluorescence Imaging
A.Skirtach et at, Nanoletters, 2005
![Page 18: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/18.jpg)
Ultrasound stimulated release.
Before - encapsulated After – released
– Power of Ultrasound for capsule rupture is compared to medical use without damage of tissues
– Higher depth of operation inside the body
Skirtach, A.G., De Geest, B.G., Mamedov, A.A., Antipov, A.A., Kotov, N.A., Sukhorukov, G.B. J. Mater. Chem., 2007, 11, 1050-1054
![Page 19: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/19.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery in living systemsIntracellular sensing
Conclusions and Perspectives
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 20: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/20.jpg)
Porous calcium carbonate microparticles (∅∅∅∅ 5µm)
������������ ������������������������������������
CaCl2
Na2CO3
+
LbL-coating CoprecipitationCore-
dissolution
Encapsulation of macromolecules after incorporaton into calcium carbonate microparticles (�coprecipitation method�)1.1.
encapsulated biopolymer
Fabrication of multicompartment „ball-in-ball“particles calcium carbonate microparticles ����
CaCO3prec. 1
CaCO3prec. 2
![Page 21: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/21.jpg)
�������������������������������������������������
ball-in-ball particle (type III)
PEM
SEM-images
ball-in-ball particle (type IV)
PEM
SEM-images
PEM
![Page 22: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/22.jpg)
step 2 LbL-coati ng
CaCO3-extraction
initial core
single-shell-capsule (mixed components)
shell-in-shell-capsule (separated components)
step 5 LbL-coati ng
ball-in-ball particle (type III) ball-in-ball particle (type IV)
~ 8 µm
ball-in-ball particle (type I) ball-in-ball particle (type II)
+ +
step 4 magnetic separation
coproduct
initial core-shell-particle
step 1 Coprecipitation
coproduct
Rhodamin-HSA
magnetite
CaCO3
Alexa 488-HSA
~ 4 µm
CaCO3
PEM
PEMPEM
���������������
unpurified raw-product
�
step 3 Coprecipitation
� 10 µm
ball-in-ball particles after magnetic
separation
Product purification by an external magnetic field.
Oliver Kreft
![Page 23: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/23.jpg)
����������� ������!����������������������
5 µm
+ E
DT
A
1 sec 2 sec 3 sec 4 sec 5 secB
ball-in-ball-particle IV
shell-in-shell capsulecore dissolution
!�����
��������
Oliver Kreft
![Page 24: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/24.jpg)
OH
H
OHH
OH
OH
HH
CH2OH
OH
N
OOH O
OH
H
OHH
OH
OH
H
CH2OH
O N
OOH OH
O CH3
����
��
����
���
Amplex Red
ResorufinD-Glucose
D-Gluconic acid-5-lactone
Principle of a coupled assay using the Amplex Red reagent. Oxidation of glucose (GOD) by glucose oxidase results in generation of H2O2, which is coupled to converion of the Amplex Red reagent to fluorescent resorufin by peroxidase (POD).
OUTER CAPSULE COMPARTMENT
INNER CAPSULE COMPARTMENT
���
���
"���������� �����������������#�����������$����������%�����������&���������� �����'()*+��������� �����'")*+
IDEA:
![Page 25: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/25.jpg)
+ A
mpl
ex R
ed 10 sec 11 sec 12 sec 13 sec
5 µm
Resorufin formation
GOD: �-D-glucose + H2O + O2 → D-gluconic acid-�-lactone + H2O2
POD: H2O2 + Amplex Red® + H+→ H2O + resorufin + CH3COOH
GODGOD
GOD
GODGOD
PODPOD
POD
Resorufin
+ G
luco
se
H2O2 formation
0 sec
�� ����� �� � �������������� ������� ���������� ��� ��� ���� ����� ������ ������� ��� ����! "��# "�������� ��������� ������� �� ��� ������������ �� ��� ������� ��������#
� �����������������#�����������$
����������%�����������&���������� �����'()*+��������� �����'")*+
Separate compartments for biochemical reactions
Kreft, O. et al. Angewandte Chemie Intern. Ed., 2007,46 (29), 5605-5608
![Page 26: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/26.jpg)
!&������!&����������������,)����-$
Mixing of reaction partners by physical triggers:
mixing
LASER
Shell doped with NP
Release of inner capsules by external trigger:
LASER
Shell doped with NPs
![Page 27: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/27.jpg)
!&������!&����������������,)����-$
AFM & SEM images of shell-in-shell microcapsules
Inner shell rupture
Outer shell rupture - release of nner capsule
O. Kreft et al, Advanced Materals, 2007, 19, 3142
![Page 28: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/28.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery into living systems Intracellular sensing
Conclusions and Perspectives
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 29: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/29.jpg)
Small 2005 1(2), 194-200
Capsules Uptake by Breast cancer cells
Capsules in cells - Artificial organellesReporting on cell interior
![Page 30: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/30.jpg)
Targeted drug delivery - Use of polymer capsules as multifunctional (magnetic, labeled) carrier systems
B. Zebli, A. S. Susha, G. B. Sukhorukov, A. L. Rogach, W. J. Parak, Langmuir, 2005, 21, 4262
A
B C
distance AC: 11 mmdistance BC: 5 mm
Magnet
CBA
![Page 31: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/31.jpg)
In cooperation with Dr. Wolfgang Parak, (LM Uni-München) Dr. Andre Skirtach
Capsules in cells - Artificial organellesRemote activation in the cells
![Page 32: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/32.jpg)
In-house developed optical setup for remote release experiments
Various sources, CCD, real-time imaging, portable, easy tranferable to new location
Andre Skirtach
![Page 33: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/33.jpg)
Optically induced release inside cells
Before
After
Skirtach, A.G., Muñoz Javier, A., Kreft, O., Köhler, K., Piera Alberola, A., Möhwald, H., Parak, W.J., Sukhorukov, G.B. Angewandte Chemie Intern. Ed., 2006, 45, 4612-4617
![Page 34: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/34.jpg)
Towards Intracellular Capsule Delivery to Neurons
In cooperation with Prof. Jo Martin and Dr. D.Davidson (Queen Mary, Neuroscience Center)
PSS/PAH capsules filled with labelled BSA
![Page 35: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/35.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery in living systemsIntracellular Sensing Systems
Conclusions and perspectives
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 36: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/36.jpg)
SNARF dyeRatiometric pH measurement. The dye shifts the maximum of the fluorescence emission from green to red color upon increasing the pH.
Emissionspectra (Fluorescence) of SN A RF-D extrane in Solution (pH 2 to 11)
0
2000
4000
6000
8000
10000
12000
510 520 530 540 550 560 570 580 590 600 610 620 630 640 650 660 670 680 690 700 710 720 730 740 750
nm
pH 2.0
pH 3.0
pH 4.0
pH 5.0
pH 6.0
pH 7.0
pH 8.0
pH 9.0
pH 10.0
pH 11.0
wavelength (nm)
inte
nsity
acidic pH: green fluorescence alkaline pH:
red fluorescenceEmissionspectra (Fluorescence) of SN A RF-D extrane in Solution (pH 2 to 11)
0
2000
4000
6000
8000
10000
12000
510 520 530 540 550 560 570 580 590 600 610 620 630 640 650 660 670 680 690 700 710 720 730 740 750
nm
pH 2.0
pH 3.0
pH 4.0
pH 5.0
pH 6.0
pH 7.0
pH 8.0
pH 9.0
pH 10.0
pH 11.0
wavelength (nm)
inte
nsity
acidic pH: green fluorescence alkaline pH:
red fluorescence
Polymer Microcapsules as Mobile Local pH-Sensor
![Page 37: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/37.jpg)
SNARF-loaded capsules change from red to green fluorescence upon internalization by MDA-MB435S breast cancer cells.
(A) SNARF-fluorescence 30 min after adding the capsules to the cell culture. (B) The same cells after another 30 min of incubation.
On-line monitoring of capsule internalisation
Kreft, O., Muñoz Javier, A., Sukhorukov, G.B., Parak, W.J. J. Mater. Chem., 2007, 42, 4471-4476
![Page 38: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/38.jpg)
Intracellular Sensors Encapsulated pH – sensor, SNARF-based dye
BeforeUptake
After Uptake
Green – low pHEmission 580nm
Inside cell endosomeRed – high pHEmission 650 mn
Outside cell
Kreft, O., Muñoz Javier, A., Sukhorukov, G.B., Parak, W.J. J. Mater. Chem., 2007, 42, 4471-4476
![Page 39: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/39.jpg)
Coating colloids and Hollow capsulesResponsive capsules
Composite capsules - Remote activationTwo compartmental capsules
Capsules delivery in living systemsIntracellular sensing
Conclusions and perspectives
Tayloring functions in microcapsules: Responsiveness and remote controlling
![Page 40: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/40.jpg)
Research strategies Research strategies
-- Design of NanoDesign of Nano--engineered shellengineered shell on colloidal particles/capsuleson colloidal particles/capsulesinc. inc. Emulsion, microEmulsion, micro-- and nanocrystals, bubblesand nanocrystals, bubblesTuning release, delivery systems into cells and tissuesTuning release, delivery systems into cells and tissues, ,
Cellreporters
enzyme functions
-- StimuliStimuli--responsive capsules responsive capsules RemoteRemote (IR(IR--, US, MW) activated release, US, MW) activated release
-- Diagnostics/Sensing using encapsulated materialDiagnostics/Sensing using encapsulated material
-- Modelling Modelling biological cellsbiological cells and organelles. and organelles. Cell residing reporters.Cell residing reporters.
![Page 41: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/41.jpg)
Macromolecule encapsulationMacromolecule encapsulation
Cell-/Tissue-Targeting
Cell-/Tissue-Targeting
Visualization, Sensors
Visualization, Sensors
Controlled release
Controlled release Remote activationRemote activation
A+B
C
MicroreactorsMicroreactors
MagnetismMagnetism
������������������������������������������������������
ProtectionProtection
![Page 42: Tayloring functions in microcapsules: Responsiveness and](https://reader034.vdocument.in/reader034/viewer/2022051000/62768469c2312e47983af64b/html5/thumbnails/42.jpg)
AcknowledgementsDr. Andre Skirtach
Dr. Oliver Kreft Dr. Christophe Dejugnat
Dr.Dmitry ShchukinDr. Tatjana Mauser Dr. Karen KöhlerDr. Alexei Antipov
Dr. Alexander PetrovDr. Tatyana Borodina
Matthieu Bedard
Prof. Dr. Helmuth Möhwald
University of Marburg – Prof. Dr. Wolfgang Parak, Dr. Almudena Muñoz Javier
University of Ghent – Dr. Bruno de Geest
NeuroScience Centre, QMUL – Prof. Jo Martin, Dr. D.Davidson