A biochemical logic approach to biomarker-activated drug release

Vera Bocharova, Oleksandr Zavalov, Kevin MacVittie, Mary A. Arugula, Nataliia V. Guz, Maxim E. Dokukin, Jan Halámek, Igor Sokolov, Vladimir Privman, Evgeny Katz

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 a 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 Fe 3+-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.

Original languageEnglish
Pages (from-to)19709-19717
Number of pages9
JournalJournal of Materials Chemistry
Volume22
Issue number37
DOIs
StatePublished - Oct 7 2012

Funding

FundersFunder number
Directorate for Engineering1066531

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