A Biochemical Logic Approach to Biomarker-Activated Drug Release, 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 drugmimicking 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 Fe-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. ________________________________________________________________________