A biochemical logic approach to biomarker-activated drug release

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 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 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. ________________________________________________________________________ An integrated system logically processing biomarkers and releasing a drug-mimicking material was developed to demonstrate a new "Sense-Act-Treat" concept.

Bridging the Two Worlds: A Universal Interface between Enzymatic and DNA Computing Systems

“…Similar release processes have been studied using enzyme systems producing citrate as the final output. [29] However, in this case the choice of potentially useful enzymes is very limited, and EnzDNA interface is not as general as the one reported in this study.…”

Insights into hydrogen bond dynamics at the interface of the charged monolayer-protected Au nanoparticle from molecular dynamics simulation

“…[12][13][14] Their surface functionality can be controlled through tailoring the composition and structure of self-assembled monolayers (SAMs), which provides a promising pathway for interpreting interactions with biomolecules. 5,[15][16][17][18][19][20][21][22] Commonly, amino acid-terminated MPANs, including carboxylic acids and amino groups, are excellent candidates for artificial proteins which can replicate desirable surface properties to unique recognition of special proteins and functional DNA.…”

Diffusion of Oligonucleotides from within Iron‐Cross‐Linked, Polyelectrolyte‐Modified Alginate Beads: A Model System for Drug Release

“…Reactive species (e.g. citrate) that form more stable complexes with Fe 3+ cations remove them from the alginate complex, and the resulting destabilization of the gel leads to its dissolution and release of the preloaded biomolecules . Citrate for triggering the release process can be produced in situ by enzymatic reactions activated by biomarkers signaling certain biomedical dysfunctions, for example, liver injury .…”

“…These composite structures offer favorable environments for embedding certain biomolecular species or/and additional gel stabilization. The added polymers were spread throughout the gel volume or, in some cases, they were used as external coatings deposited layer‐by‐layer on the gel surface . Depending on the specific composition of the alginate systems (e.g.…”