Biodynamers: applications of dynamic covalent chemistry in single-chain polymer nanoparticles

Dynamic Covalent Chemistry (DCC) enables the development of responsive molecular systems through the integration of reversible bonds at the molecular level. These systems are thermodynamically stable and capable of undergoing various molecular assemblies and transformations, allowing them to adapt to changes in environmental conditions like temperature and pH. Introducing DCC into the field of polymer science has led to the design of Single-Chain Nanoparticles (SCNPs), which are formed by self-folding via intramolecular crosslinking mechanisms. Defined by their adaptability, SCNPs mimic biopolymers in size and functionality. Biodynamers, a subclass of SCNPs, are specifically designed for their stimuli-responsive and tunable, dynamic properties. Mimicking complex biological structures, their scope of application includes target-specific and pH-responsive drug delivery, enhanced cellular uptake and endosomal escape. In this manuscript, we discuss the integration of DCC for the design of SCNPs, focusing particularly on the characteristics of biodynamers and their biomedical and pharmaceutical applications. By underlining their potential, we highlight the factors driving the growing interest in SCNPs, providing an overview of recent developments and future perspectives in this research field.