Assembly and Characterization of Polyelectrolyte Complex Micelles

Abstract

Polyelectrolyte complex micelles (PCMs), core-shell nanoparticles formed by selfassembly of charged polymers in aqueous solution, provide a powerful platform for exploring the physics of polyelectrolyte interactions and also offer a promising solution to the pressing problem of delivering therapeutic oligonucleotides in vivo. Developing predictive structure-property relationships for PCMs has proven difficult, in part due to the presence of strong kinetic traps during nanoparticle self-assembly. This article discusses criteria for choosing polymers for PCM construction and provides protocols based on salt annealing that enable assembly of repeatable, low-polydispersity nanoparticles. We also discuss PCM characterization using light scattering, small-angle X-ray scattering, and electron microscopy. Polymer selection and preparationPCM properties are strongly influenced by the physical and chemical characteristics of the constituent polymers, making polymer selection a critical step in the design process. The most well-characterized block copolymers for nucleic acid PCMs are linear diblocks such as poly(lysine)-poly(ethylene glycol) (pLys-PEG), but PCMs can be formed between polyelectrolytes and a variety of hydrophilic neutral-charged polymers, which can be

Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles

“…presence of PMPC likely contributes to a larger RGuinier due to increased corona scattering and to a larger Rh (and larger, more hydrated corona) due to the disruption of hydrogen bonding formation between water molecules [26]. Furthermore, longer cationic blocks formed larger micelle cores throughout this study, consistent with previous reports [55,59,63] of micelle size being solely dependent on the charged block length of the block polymer and independent of homopolymer length. Figure 5.…”

“…Data were reduced in MATLAB at the beamline. Background subtraction and fitting were performed using the multi-level modeling macros distributed with the Irena software package (Release 2.67) [58] for Igor Pro (Version 7.08) as described in Ref [59].…”

Physical Property Scaling Relationships for Polyelectrolyte Complex Micelles

“…These materials reflect commonly used model systems and PCMs used for oligonucleotide delivery and the range of polymer lengths exceeds those that have shown promising for biomolecular applications. We assembled all PCMs by slowly removing high concentration salt through dialysis to ensure a near-equilibrium state 28,40 . We used SAXS and DLS to determine the core size, hydrodynamic size, and aggregation number for all samples.…”

“…Background subtraction and model fitting were performed using the multi-level modeling macros distributed with the Irena software package 55 for Igor Pro as described previously. 28 We use assume a Shulz-Zimm distribution and a rigid spheroid shape factor when modeling SAXS data to gather core radius, aspect ratio, and particle size polydispersity (Table S2). While these are core-shell nanoparticles, core-shell shape factors are not appropriate in this situation because the corona is transparent via SAXS.…”

Physical Property Scaling Relationships for Polyelectrolyte Complex Micelles

“…Background subtraction and model fitting were performed using the multi-level modeling macros distributed with the Irena software package 55 for Igor Pro as described previously. 28 We use assume a Shulz-Zimm distribution and a rigid spheroid shape factor when modeling SAXS data to gather core radius, aspect ratio, and particle size polydispersity (Table S2). While these are core-shell nanoparticles, core-shell shape factors are not appropriate in this situation because the corona is transparent via SAXS.…”