Polyelectrolyte complex micelles (PCMs) offer a promising platform for oligonucleotide delivery; however, conventional preparation methods based on block copolymers require chemical modification of either the oligonucleotide cargo or the cationic carrier polymer. Here, we report a modified strategy for PCM formation in which the ends of target DNAs (tDNAs) are hybridized with poly(ethylene glycol)-conjugated DNA (DNA-PEG) helper molecules to generate diblock and triblock pseudoblock copolymers (pseudo-BCPs). These pseudo-BCPs are subsequently complexed with branched polyethylenimine (BPEI) to form PCMs. Pseudo-BCPs bearing PEG chains of 5 kg/mol (pseudo-BCP(5k)) or greater yield PCMs with well-defined core-shell morphologies and exhibit excellent temporal stability and salt resistance. In vitro analyses using cultured cells demonstrate that all PCM systems show enhanced cellular uptake relative to free tDNA, with pseudo-BCP(5k)-derived PCMs exhibiting the highest efficiency. These results establish pseudo-BCP-based PCM assembly as a feasible new route to prepare nanocarriers for oligonucleotide delivery.
Lee et al. (2026) studied this question.