A Biochemical Logic Approach to Biomarker-Activated Drug Release

TL;DR

This study develops a biochemical logic system that detects liver injury biomarkers ALT and AST to trigger targeted drug release from microspheres, demonstrating potential for smart, disease-specific drug delivery.

Contribution

It introduces a biocatalytic cascade implementing a Boolean AND gate for biomarker detection and controlled drug release, integrating signal processing with drug delivery.

Findings

Dye release occurs only at high ALT and AST concentrations.

The system differentiates low vs. high biomarker levels effectively.

Single microsphere analysis reveals release kinetics.

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 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.