Designing DNA nanostar hydrogels with programmable degradation and antibody release

TL;DR

This study systematically investigates how the structural design of DNA nanostar hydrogels influences their degradation and antibody release, enabling programmable, enzyme-responsive drug delivery systems.

Contribution

It provides a quantitative understanding of design parameters controlling hydrogel degradation and demonstrates enzyme-specific control over cargo release.

Findings

Removing flexible joints accelerates degradation

Increasing arm length speeds up hydrogel breakdown

Relocating restriction enzyme sites enhances degradation rate

Abstract

DNA nanostar (DNAns) hydrogels are promising materials for in vivo applications, including tissue regeneration and drug and antibody delivery. However, a systematic and quantitative understanding of the design principles controlling their degradation is lacking. Here, we investigate hydrogels made of three-armed DNAns with varying flexible joints, arm lengths, and mesh sizes and use restriction enzymes to cut the DNAns structures while monitoring the gel's degradation. We discover that (i) removing flexible joints, (ii) increasing arm length, or (iii) relocating the RE site along a DNA linker markedly accelerates hydrogel degradation. In contrast, non-specific endonucleases, e.g. DNaseI, quicly degrade DNAns hydrogels regardless of design. Importantly, the release of antibodies from DNAns hydrogels can be modulated by the action of different enzymes, confirming that programmable degradation can be leveraged for responsive drug-delivery systems. These findings provide a better understanding of the design principles for DNAns-based scaffolds with tunable degradation, cargo release, and responsive rheology.