Nanoimprint Lithography Based Fabrication of Shape-Specific Enzymatically-Triggered Smart Nanoparticles Jeffrey Chou EE235 Papers Reviewed  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.  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 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.