(193bg) Mechanism of Dissociation Kinetics in Polyelectrolyte Complex Micelles

Polyelectrolyte complex (PEC) micelles form when oppositely charged block polyelectrolytes are mixed together in aqueous media. The polyelectrolyte blocks, driven by electrostatic interaction, associate and phase separate, leading to a dense and polymer-rich PEC core stabilized by a neutral block corona. Compared to amphiphilic micelles, these nanoscale PEC micelles have significant advantages in various biomedical applications including RNA therapeutic delivery, tissue engineering, and diagnostics. The formation and dissociation kinetics of amphiphilic micelles have been demonstrated by stopped-flow light scattering, and very recently the growth kinetics of bulk polyelectrolyte complexes has been studied using time-resolved SAXS (TR-SAXS). The time scales of these processes range from a few milliseconds to thousands of milliseconds.

So far, no work has been reported on the dissociation kinetics of polyelectrolyte complex micelle systems. The cargo is believed to be released by introducing environmental triggers, e.g. salt. Herein, we have study comprehensively the kinetic pathways of the dissociation behaviors in PEC micelles when salt is added using a combination of techniques, including time-resolved small-angle X-ray scattering, laser light scattering, Cryo-TEM and liquid-cell TEM. We found that, surprisingly, the kinetic pathway in PEC micelles is primarily governed by micelle fragmentation, which is opposite to the single-chain expulsion mechanism in amphiphilic micelles. Moreover, we found that the time scale of PEC micelle dissociation ranges from minutes to hours, which is significantly slower than this of amphiphilic micelles. In addition, we also investigated the effect of salt concentration and temperature on the relaxation kinetics of PEC micelles. We believe these discoveries will enhance our understanding of the complexation-driven assembly/disassembly processes and shed light on gene delivery. Moreover, understanding the intricate nuances allows better design of polyelectrolyte complex based materials for biomedical application.