Aptamer Functionalized DNA Hydrogel for Wise-Stage Controlled Protein Release

Chen Liu,Jialun Han,Jie Du,Yuxuan Pei

doi:10.3390/app8101941

Abstract

With the simple functionalization method and good biocompatibility, an aptamer-integrated DNA hydrogel is used as the protein delivery system with an adjustable release rate and time by using complementary sequences (CSs) as the biomolecular trigger. The aptamer-functionalized DNA hydrogel was prepared via a one-pot self-assembly process from two kinds of DNA building blocks (X-shaped and L-shaped DNA units) and a single-stranded aptamer. The gelling process was achieved under physiological conditions within one minute. In the absence of the triggering CSs, the aptamer grafted in the hydrogel exhibited a stable state for protein-specific capture. While hybridizing with the triggering CSs, the aptamer is turned into a double-stranded structure, resulting in the fast dissociation of protein with a wise-stage controlled release program. Further, the DNA hydrogel with excellent cytocompatibility has been successfully applied to human serum, forming a complex matrix. The whole process of protein capture and release were biocompatible and could not refer to any adverse factor of the protein or cells. Thus, the aptamer-functionalized DNA hydrogel will be a good candidate for controlled protein delivery.

Highlights

Protein drugs with uncontrolled dosage can usually cause severe side effects such as the incidence of complications in normal tissues and organs, despite their outstanding treating function in different types of human diseases [1]
The results indicated that X-DNA and L-DNA formed as designed, and the pure single band that was shown in lanes 5 and 8 demonstrated that the assembly processes were highly efficienct
Due to the specific bind of thrombin to the aptamer in the hydrogel. These results demonstrated that the hydrogels without aptamers had a very low protein capture capacity just because of the physical diffusion effect

Summary

Introduction

Protein drugs with uncontrolled dosage can usually cause severe side effects such as the incidence of complications in normal tissues and organs, despite their outstanding treating function in different types of human diseases [1]. The localized and controlled release of protein drugs has been achieved in many research studies. In the drug and gene release systems, hydrogels were widely used as stimuli-responsive materials because of their responsiveness to external stimuli such as light, temperature, pH, metal ions, or other molecules [2,3,4,5]. Hydrogel functionalization has been extensively studied to improve the effectiveness of its sustained release. The incorporation of different affinity ligands such as metal ion chelating ligands [7], heparin or heparan sulfate [8,9,10], and streptavidin or biotin [11] into hydrogels have been widely used to improve the affinity of hydrogels with protein drugs and overcome burst release. Sakiyama–Elbert et al have designed a heparin-based system to immobilize neurotrophin-3 in the fibrin gel by non-covalent interaction to rein in the diffusion-based release of

Methods

Results

Conclusion