Transcript Shuyi Li`s slides_2010 - Annual Unither Nanomedical

Porous-Wall Hollow Glass Microsphere
as novel potential nanocarriers for
biomedical applications
Shuyi Li, M.D., Ph.D.
NIH Nanomedicine Center for Nucleoprotein Machines
Institute of Molecular Medicine and Genetics
Medical College of Georgia, USA
3rd Annual Unither Nanomedical & Telemedical
Technology Conference, Orford, Canada
February 23 -26, 2010
Background information
1.
History: two decades, one million patients.
2.
Applications: dental, orthopedic, and tissue
engineering.
3.
Recent example: tumor treatments (solid glass
microsphere + Yttrium (90Y) radio isotope).
4.
Current strategy: bonding to organic polymers or
the deposition of chemical substances directly into
the glass matrix.
5.
Our strategy: development of a more general
approach for drug delivery Porous-Wall Hollow
Glass Microsphere (PW-HGMs)
Background information
Example: liver cancer treatment with 90Y glass microsphere
Biomed Imaging Interv J 2006; 2(3):e43
Our Goal and Strategy
Our Goal:
To develop a novel drug carrier
•
Higher dose delivery of
bioactive agents
•
Prolonged or controlled release
•
Versatile drug delivery capability
(chemot drugs, antibodies,
siRNA, radio isotope or other
macromolecules individually or
in combination)
Our Strategy:
•
Glass microsphere, not regular
glass
Introduction to PW-HGMs
• Safe: same as bioglass
• PW-HGMs have higher delivery
capacity than solid glass
microsphere.
• Porous wall allows controlled
release of biological molecules
such as antibody proteins, and
siRNA
• Able to delivery different reagents.
PW-HGMs and its Shell
Shuyi Li, et al., Nanomedicine 6:127–136 (2010)
Interaction of dextrans, nucleic acids,
and proteins with PW-HGMs
Shuyi Li, et al., Nanomedicine 6:127–136 (2010)
What is size exclusion limit of PWHGMs?
Size exclusion limit: 8.5 ~14.4 nm
FITC-Dextran:200 g/ml
Shuyi Li, et al., Nanomedicine 6:127–136 (2010)
Can PW-HGMs be a carrier for
nucleic acids?
• Both DNA oligonucleotide and
siRNA can enter interior cavity.
• 70-kDa dextran can be used to
“gate” siRNA.
• Internalized siRNA shows controlled
release.
Shuyi Li, et al., Nanomedicine 6:127–136 (2010)
Can PW-HGMs be a carrier for
protein?
• PW-HGMs can be used as
carries for proteins, antibodies,
and antibody fragments.
• Antibody shows controlled
release.
• Delivered antibody fragments
are functional.
Shuyi Li, et al.,
Nanomedicine 6:127–136 (2010)
Can PW-HGMs be a carrier for
intratumoral injection?
• Quantitative image analysis
revealed a linear relationship
between the amount of material
loaded and the corresponding
photon counts.
• PW-HGMs are retained at the
site of intratumoral injection and
thus could be used for localized
delivery of antitumor antibodies or
siRNA.
Shuyi Li, et al.,
Nanomedicine 6:127–136 (2010)
CONCLUSIONS
1.
PW-HGMs are a novel form of glass material consisting of a hollow
central cavity with 1 micron-thick wall, which has tortuous network of
nanometer-scale channels.
2.
The porous walls of PW-HGMs promote size-dependent uptake and
controlled release of biological molecules in the 3-8 nm range. This
includes antibodies and a modified single-chain antibody fragment
which are released functional.
3.
The 70 kDa dextran can be used to gate the porous walls, facilitating
controlled release of an internalized siRNA.
4.
Dextran loaded with PW-HGMs remained in place after mouse
intratumoral injection, suggesting a possible application for drug
delivery of anti-cancer drugs.
5.
The results suggest that PW-HGMs have potential as novel
nanocarriers for antibodies, recombinant antibody derivatives, and
small oligonucleotides.
Acknowledgement
Medical College of Georgia
William S. Dynan
Hairong Xiong
Tom Hu
Jin-Xiong She
Savannah River National Laboratory
George G. Wicks
Steven M. Serkiz
Something colorful
Augusta, GA, USA
Thank you
Institute of Molecular Medicine and Genetics
Augusta, GA, USA