Nanoimprint Lithography Based Fabrication of Shape-Specific Enzymatically-Triggered Smart Nanoparticles

Jeffrey ChouEE235

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

Enzyme Release

Drug Encapsulation

PEGDAInsert to Cells

Nanoimprint Fabrication

1)PEGDA Applied to silicon

2)Quartz template pressed onto PEGDA

3)Remove template4)Oxygen etch to

remove residual layer5)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

Enzyme Release

Drug Encapsulation

PEGDAInsert to Cells

ConclusionDemonstrated 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.