Investigating the Self-Assembly of Polyelectrolyte Complex Micelles from Single-Stranded Oligodeoxynucleotide-Poly(ethylene glycol) Conjugates and Polyethylenimine

Single-stranded oligodeoxynucleotide-poly(ethylene glycol) (ssODN-PEG) conjugates with varying ssODN and PEG lengths are synthesized and complexed with polyethylenimine (PEI) to form polyelectrolyte complex micelles (PCMs). The conjugation of PEG chains has a minor impact on ssODN binding; however, PEG chains of extended length can hinder ion pairing due to steric effects. The complexation of ssODN-PEG with branched PEI (BPEI) leads to the self-assembly of spherical core–shell PCMs. When PEG chains are too short relative to the complexed core, aggregation of the PCMs occurs, evidenced by a deviation from the spheroid form factor and a rapid increase in the hydrodynamic size over time. The complexation of ssODN-PEG with linear PEI (LPEI) is also investigated. In phosphate-buffered saline (PBS) at physiologically relevant ionic strength, LPEI exhibits significantly weaker binding to ssODN-PEG compared to BPEI. However, well-defined PCMs are formed in either salt-free water or NaCl solutions, highlighting the strong ion sensitivity of LPEI-mediated complexation.