Polyelectrolyte complex micelles (PCMs) are a unique class of self-assembled nanoparticles that form with a core of associated polycations and polyanions, microphase-separated from neutral, hydrophilic coronas in aqueous solution. The hydrated nature and structural and chemical versatility make PCMs an attractive system for delivery and for fundamental polymer physics research. By leveraging block copolymer design with controlled self-assembly, fundamental structure–property relationships can be established to tune the size, morphology, and stability of PCMs precisely in pursuit of tailored nanocarriers, ultimately offering storage, protection, transport, and delivery of active ingredients. This perspective highlights recent advances in predictive PCM design, focusing on (i) structure–property relationships to target specific nanoscale dimensions and shapes and (ii) characterization of PCM dynamics primarily using time-resolved scattering techniques. We present several vignettes from these two emerging areas of PCM research and discuss key opportunities for PCM design to advance precision medicine.

DNA has been used as probes for nanopore sensing of noncharged biomacromolecules due to its negative phosphate backbone. Inspired by this, we explored the potential of diblock synthetic polyelectrolytes as a more flexible and less expensive nanopore sensing probe by investigating translocation behaviors of PEO-b-PSS and PEO-b-PVBTMA through commonly used alpha-hemolysin (α-HL) and Mycobacterium smegmatis porin A (MspA) nanopores. Translocation recordings in different configurations of pore orientation and testing voltage indicated efficient PEO-b-PSS translocations through α-HL and PEO-b-PVBTMA translocations through MspA. This work provides insight into synthetic polyelectrolyte-based probes to expand probe selection and flexibility for nanopore sensing.

Polyelectrolyte complex micelles are hydrophilic nanoparticles that self-assemble in aqueous environments due to associative microphase separation between oppositely charged blocky polyelectrolytes. In this work, we employ a suite of physical characterization tools to examine the effect of charged block length mismatch on the equilibrium structure of double diblock polyelectrolyte complex micelles (D-PCMs) by mixing a diverse library of peptide and synthetic charged-neutral block polyelectrolytes with a wide range of charged block lengths (25–200 units) and chemistries. Early work on D-PCMs suggested that this class of micelles can only be formed from blocky polyelectrolytes with identical charged block lengths, a phenomenon referred to as chain length recognition. Here, we use salt annealing to create PCMs at equilibrium, which shows that chain length recognition, a longstanding hurdle to repeatable self-assembly from mismatched polyelectrolytes, can be overcome. Interestingly, D-PCM structure–property relationships display a range of values that vary systematically with the charged block lengths and chemical identity of constituent polyelectrolyte pairings and cannot be described by generalizable scaling laws. We discuss the interdependent growth behavior of the radius, ionic pair aggregation number, and density in the micelle core for three chemically distinct diblock pairings and suggest a potential physical mechanism that leads to this unique behavior. By comparing the results of these D-PCMs to the scaling laws recently developed for single diblock polyelectrolyte complex micelles (S-PCMs: diblock + homopolymer), we observe that D-PCM design schemes reduce the size and aggregation number and restrict their growth to a function of charged block length relative to S-PCMs. Understanding these favorable attributes enables more predictive use of a wider array of charged molecular building blocks to anticipate and control macroscopic properties of micelles spanning countless storage and delivery applications.