Engineering target-responsive hydrogels based on aptamer-target interactions

Abstract

In this communication, we report a simple, but highly adaptable, method of constructing selective target-responsive hydrogels using DNA aptamers. The simplicity of the design is accomplished by using linear polymer chains as the hydrogel backbone and a DNA aptamer as the cross-linker. In this design, competitive binding of target to the aptamer causes the decrease of cross-linking density and, hence, dissolution of the hydrogel. The adaptability of this strategy for therapeutic applications was demonstrated using two different types of targets, small molecules and proteins. Our results indicated that this molecular engineering provides a highly selective and controllable release system whereby efficient release of therapeutic agents can occur at specific environments in which the target biomarker is found.

Figure 1

(a) Scheme of DNA-induced formation and adenosine-induced dissolution of hydrogel: (I) Add LinkerAdap to bind to Strand A- and Strand B-incorporated polyacrylamide mixture to form the hydrogel. (II) Add adenosine to competitively bind LinkerAdap to dissolve the hydrogel. (b) DNA sequences and linkages in the hydrogel. Optical images of the sol-gel transition: (c) system in the fluid state before LinkerAdap was added; (d) system in the gel state after LinkerAdap was added; and (e) system reverting to the initial fluid state after adenosine was added. In a control experiment, a mutated linker with the two mutations, as shown in (b) by the two short black arrows, was used.

Figure 2

Absorption measurements of gold NPs in the gel systems. (Left) Cross-linked hydrogel with entrapped gold NPs disassembles upon addition of the target adenosine and dispenses the gold NPs into the buffer solution. There was little absorption in the beginning because the gold NPs are trapped inside the gel. Increasing absorbance was monitored after adenosine was added to the gel system as the gold NPs were released from the gel into the solution. The absorption was obtained with a spectrometer in constant-wavelength mode. (Right) Photograph of gels with entrapped gold NP is on the left, and the one on the right is the system 15 min after the addition of adenosine.

Scheme 1