Wednesday, May 1, 2013

1304.8000 (V. Bocharova et al.)

A Biochemical Logic Approach to Biomarker-Activated Drug Release    [PDF]

V. Bocharova, O. Zavalov, K. MacVittie, M. A. Arugula, N. V. Guz, M. E. Dokukin, J. Halamek, I. Sokolov, V. Privman, E. Katz
The present study aims at integrating drug-releasing materials with signal-processing biocomputing systems. Enzymes alanine transaminase (ALT) and aspartate transaminase (AST)---biomarkers for liver injury---were logically processed by a biocatalytic cascade realizing Boolean AND gate. Citrate produced in the system was used to trigger a drug-mimicking release from alginate microspheres. In order to differentiate low vs. high concentration signals, the microspheres were coated with a protective shell composed of layer-by-layer adsorbed poly(L-lysine) and alginate. The alginate core of the microspheres was prepared from (Fe3+)-cross-linked alginate loaded with rhodamine 6G dye mimicking a drug. Dye release from the core occurred only when both biomarkers, ALT and AST, appeared at their high pathophysiological concentrations jointly indicative of liver injury. The signal-triggered response was studied at the level of a single microsphere, yielding information on the dye release kinetics.
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