Fuyuhiko Tamanoi Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, USA. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan.
Implementation of histopathological techniques and transmission electron micr...
Ähnlich wie Fuyuhiko Tamanoi Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, USA. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan.
Ähnlich wie Fuyuhiko Tamanoi Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, USA. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan. (20)
Module for Grade 9 for Asynchronous/Distance learning
Fuyuhiko Tamanoi Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, USA. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan.
1. Fuyuhiko Tamanoi
Professor
Dept. of Microbio., Immunol. & Molec. Genet.
UCLA
Professor
Institute for Integrated Cell-Material Sciences
Kyoto University
Cancer Therapy using Mesoporous Silica Nanoparticles
iCEMS, Kyoto UniversityUCLA
2. Mesoporous Silica Nanoparticles as a vehicle
for targeted delivery of anticancer drugs
Current
Chemotherapy
Nanoparticle
based therapy
Jeff
Zink
3. Mesoporous Silica Nanoparticles
40 nm
- Homogeneous preparation
- Diameter is 130 nm
- 1400 pores/particle
- Pore diameter is 2 nm
- Large scale preparation
- Well established chemistry can be used to modify
surface or to attach nanomachines
4. Si
O
O
Si
Si
O
Si
O
O
Si
Si
O
O
Si
O
O
O
O
O
O
O
NH3
+
Si
O
-
Si
Si
O
O
P
-
O
O
P
O
-
O
2 nm
F CPT
F
F
FCPT
F = FITC CPT = camptothecin
Si
O
O
Si
Si
O
Si
O
O
Si
Si
O
O
Si
O
O
O
O
O
O
O
NH3
+
Si
O
-
Si
Si
O
O
P
-
O
O
P
O
-
O
2 nm
FF CPT
FF
FF
FFCPT
F = FITC CPT = camptothecin
Apoptosis
MSNs provide valuable delivery
vehicles for hydrophobic, water-
insoluble anticancer drugs
(camptothecin, taxol etc).
Camptothecin
Anticancer drugs can be loaded into the pore
Phosphonate
surface
modification
5. Size of nanoparticles that
can benefit from EPR:
40 - 400 nm
Nanoparticles can accumulate in the tumor
Passive targeting (Enhanced permeability retention)
Active targeting
Surface modification
of NP with targeting
moiety
Normal
tissue Tumor
Folic Acid Silica NanoparticleFolic Acid Silica NanoparticleFolic Acid Silica NanoparticleFolic Acid Silica Nanoparticle
9. Controlled Release
Zero premature release
On-command Release
External
stimuli
Local release
Spatial and temporal
control
Towards
Non-invasive therapy
In collaboration with
Jeffrey Zink
Fraser Stoddart
Light
Magnetic field
10. Development of external signal responsive nanoparticles
NanovalveNanovalve
“Open and Close”
Rotaxanes consist of a
stalk and a moving part
Nanovalve
Nanoimpeller
11. Nanoimpellers
Photo-responsive azobenzene motion in the pores of nanoparticles
CisTrans
Ground state Excited state
Photon
Photon
Motion is generated by light
exposure
Azobenzene
Large conformational change
occurs upon light exposure
12. N N N
N N
N N NN N
457nm
Photo-responsive azobenzene motion in the pores of nanoparticles
= Fluorescent dyes/anticancer drugs
N N
N
N
N
Nanoimpeller
13. Light induced release of
anticancer drug (CPT)
from nanoimpeller in cells
Nucleus
light
release
Cancer cell
MSN
Nucleus
light
release
Cancer cell
MSN
Nucleus
light
release
Cancer cell
MSN
Cell culture chamber
Blue Laser
Cell culture chamber
Blue Laser
0.1 W/cm2
Exposure time dependent release of anticancer drugs.
Power dependent release of anticancer drugs.
Repeated exposure and anticancer release can be achieved.
Cell killing (apoptosis)
14. Magnetic
property
for movement,
recovery
Iron oxide core
Mesoporous
silica
Magnetic nanoparticles
Iron oxide core
MSNs
a b c d ea b c d ea b c d e
H2O MSNs
Iron-oxide MSNs
4 2 1 mg/ml
MRI enhancing effect
15. Magnetic field responsive nanovalves
Superparamagnetic
property of iron oxide
Magnetic nanoparticles heat up when
exposed to oscillating magnetic field.
Magnetic
field
16. No exposure
5 min exposure
Exposure of doxorubicin loaded NPs to oscillating magnetic field
results in drug release and killing of human cancer cells
Release of Dox Cell killing
Doxorubicin-loaded Mag-
MSN is taken up into breast
cancer cells MDA-MB-231.
Frequency 500 KHz
Amplitude 37.4 KAm-1
18. Clinical potential to use magnetic field
Apply magnetic coil to generate
oscillating magnetic field
Alternating magnetic field applicator
NanoActivator F100
Targeted magnetic field
Overlay focusing magnetic
effect on top of oscillating
magnetic field
19. We have studied a new type of mesoporous silica
nanoparticles that have enhanced biodegradation
Proteases,
Reducing
conditions
Safety of materials is a paramount concern when
envisioning clinical application
20. Incorporating organic bonds into the framework
Sol-gel synthesis
Pore
CTAB
Alkali
Periodic mesoporous organosilica
Si
OR
OR
OR
RO
Pore
CTAB
Alkali
Pore
Pore
Mesoporous silica NPs
tetraalkoxysilane
Bridged alkoxysilane
23. Biodegradable PMOs are effective in drug delivery
Drug delivery to inhibit
cancer cell growth
Cancer cell uptake Uptake of FITC-labeled NPs
into PANC-1 cells
31. Chicken Egg model vs Mouse Model
Chicken egg Mouse
Short experimental assay (days) Longer observation period
3 days for tumor formation! (weeks to months)
Economical
Expensive
50 yen per egg! 10,000 yen per mouse
High throughput Laborious
Animal protocol not needed! Extensive animal review
40. 1. Biodegradable PMO nanoparticles provide a
promising type of MSN for cancer therapy.
2. Various biodegradable bridges can be
incorporated.
3. Further animal experiments are being carried
out.
42. Chicken egg tumor model provides a valuable
addition to Precision Medicine
Patient derived
tumor model
Identify optimized
Treatment for each patient
Tailor made
treatments
5 days 5 days
Drug screening
Sensitivity screen
Radiation, PDT, hyperthermia
43. Jean-Olivier Durand
Fraser Stoddart
Michael Ambrogio
Fuyuhiko Tamanoi
Kotaro Matsumoto
Tan Doan
Takehiro Harada
Keigo Nakai
Binh Vu
Joel Hayashi
Tammy Yik
Jeff Heard
Northwestern University
University of Montpellier
Jeffrey Zink
Juyao Dong
Angela Hwang
Courtney Thomas
Dan Ferris
City of Hope Cancer Center
Carlotta Glackin
James Finlay
Cai Roberts
Sophia Shahin
King Abdulah University of Science
and Technology
Jonas Croissant
Niveen Khashab
iCEMS, Kyoto University
UCLA