Enzyme-responsive DNA smart materials for biomedical applications

Abstract

Deoxyribonucleic acid (DNA) has emerged as a highly programmable, biocompatible and structurally versatile building block for the construction of multifunctional biomaterials, presenting broad application potential in biomedicine. With advances in DNA nanotechnology, dynamic DNA architectures responsive to various stimuli such as pH, temperature, light, ions and enzymes, have been developed. Among these stimuli, enzymes are particularly promising triggers due to their abundant presence in physiological and pathological contexts, where their expression or activity is often altered in disease states. Enzyme-responsive DNA smart materials, designed to exploit endogenous enzymes or delivered exogenous enzymes, enable disease-specific targeting, spatiotemporally controllable drug release, and sensitive diagnostic detection. This review outlines the structural and functional characteristics of enzymes relevant to DNA materials and summarizes the design principles for engineering enzyme-responsive DNA smart materials. We then survey the types and the latest advances of enzyme-responsive DNA smart materials, focusing on their applications in drug delivery, diagnosis and biosensing, cell regulation and tissue engineering. Finally, we discuss current challenges and future directions for the development of enzyme-responsive DNA smart materials in translational biomedicine.