Transcript Nanoimprint Lithography Based Fabrication of Shape

Nanoimprint Lithography Based Fabrication of
Shape-Specific Enzymatically-Triggered Smart
Nanoparticles
Jeffrey Chou
EE235
Papers Reviewed
[1] Luz Cristal Glangchai, Mary Caldorera-Moore, Li Shi, Krishnendu Roy,
Nanoimprint lithography based fabrication of shape-specific, enzymatically-triggered
smart nanoparticles, Journal of Controlled ReleaseVolume 125, Issue 3, , 11 February
2008, Pages 263-272.
[2] J.A. Champion, Y.K. Katare and S. Mitragotri, Particle shape: a new design parameter
for micro-and nanoscale drug delivery carriers, J. Control. Release 121 (1–2) (2007), pp.
3–9.
Basic Idea
PEGDA
Insert to Cells
Enzyme Release
Drug Encapsulation
Nanoimprint Fabrication
1) PEGDA Applied to silicon
2) Quartz template pressed
onto PEGDA
3) Remove template
4) Oxygen etch to remove
residual layer
5) Particles harvested by water
buffer.
Shape Variability for Delivery
-Shape form factors, aspect
ratios, or edges affect particle
transport.
- Eg: Cell membrane
interaction is heavily dependent
on shape of particle.
50nm -> 400nm particles
Shape Dependence
-With nanoimprint, a wide variety of
shapes and depth can be made for custom
drug delivery.
Drug Encapsulation
-Fluorescently labeled
antibodies were trapped within
400nm nanocarriers.
- After releasing, particles
remained intact by retaining its
fluorescence.
- Shows that encapsulation
does not degrade drug
Enzyme Based Release
-PEGDA is mixed with an
enzymatically degradable peptide
GFLG
- GFLG Sensitive to Cathepsin B
enzyme
-Which is present in lung, ovarian,
and colorectal tumor cells.
- Other peptides can be used for
other diseases
- Eg: Breast cancer cells have high
concentrations o f Cathepsin D
enzyme
Enzyme Release
Cathepsin B based biodegradable
encapsulation
-(a) No Cathepsin B
- (b) 30min. In Cathepsin B
- (c) 12h in Cathepsin B
- (d) 48h in Cathepsin B
Basic Idea
PEGDA
Insert to Cells
Enzyme Release
Drug Encapsulation
Conclusion
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Demonstrated the potential for enzyme based nano
drug delivery method for cells.
PEGDA and drugs can be easily mixed.
Nanoimprint allows for small particles (~50nm) to be
internalized by cells.
Enzyme based release allows for “smart” drug delivery.