Polyplexes

Polyplexes are nanoscale complexes formed by the electrostatic assembly of polyelectrolytes, typically a cationic polymer with a negatively charged nucleic acid such as DNA or RNA. This interaction condenses the nucleic acid into compact particles, protects it from nuclease degradation, and enhances cellular uptake compared with free nucleic acids. The composition is mainly a polycationic polymer and the nucleic acid; common polymers include polyethyleneimine (PEI), poly-L-lysine, chitosan, poly(beta-amino esters), and PAMAM dendrimers.

Formation is usually accomplished by mixing polymer and nucleic acid in aqueous solution at defined nitrogen-to-phosphate (N/P) ratios, driving electrostatic complexation. Resulting polyplexes typically range from 20 to 200 nm and bear a positive surface charge, though surface tuning through shielding or adsorption of serum proteins can modify size and zeta potential in biological media.

Function and mechanism: after administration, polyplexes interact with cell membranes, are internalized (often by endocytosis), and, in some cases, escape endosomes (for example via the proton sponge effect associated with certain polycations) to release nucleic acids into the cytoplasm. Applications emphasize non-viral gene delivery, including plasmid DNA, siRNA, mRNA, and combinations for co-delivery; they are also explored for drug delivery and as building blocks in tissue engineering.

Strengths include low immunogenicity compared with viral vectors, tunable properties, and relative ease of production. Limitations include cytotoxicity of many cationic polymers (notably high molecular weight PEI), limited stability in serum, potential aggregation, and manufacturing and regulatory challenges. Researchers address these by using biodegradable or lightly cationic polymers, by shielding with poly(ethylene glycol) or polysaccharides, and by incorporating targeting ligands to improve specificity.

Overall, polyplexes constitute a versatile platform in gene delivery and interdisciplinary biomaterials research, with ongoing work to balance efficiency, safety, and manufacturability.