Molecular engineering strategies for designer polyelectrolyte nanocomplexes

Statement of Purpose: Polyelectrolyte complex assemblies comprise unique ion-containing macromolecules that are poised to advance the encapsulation and delivery capabilities of challenging therapeutic biomolecules, such as nucleic acids, peptides, or proteins.¹ Such vehicles can be advantageously engineered to react and adapt to physiological stimuli, such as changes in pH, ionic strength, enzyme, or temperature.² However, for modern biomaterials, a rigorous understanding how chemical and ionic character relate to physical laws in hierarchical charged assemblies has been elusive. A materials– genome approach, centered on the systematic expansion of tailored polyelectrolytes, can elucidate how specific non-covalent interactions prevail in self-assembly and behavior toward bioapplications. In this work, we demonstrate this idea with a series of designer polyelectrolyte complexes, from bulk complex coacervates to nanocomplex micelles and gels (Fig. 1). The formation, structural evolution, and stability of these complex assemblies were studied as a function of design parameters, demonstrating their versatility as emerging materials in advanced drug delivery, regenerative medicine, underwater adhesives, and water purification.