Nanoparticles based on the cyclopropenium cation

Cationic polymers offer a wide range of biomedical applications, and so their development is of paramount importance. We have prepared a series of novel polymers bearing cationic cyclopropenium either along a polyester backbone, or as a tri-functional crosslinker of secondary amine-containing polymers. When dispersed in aqueous media, polymers form spherical nanoparticles with high positive charge that is maintained even in alkaline conditions due to the permanent positive charge afforded by the cyclopropenium cation. These particles have displayed important biological effects, particularly as gene transfection vectors or as antimicrobial agents.

Non-viral vectors for the transfection of genetic material are at the frontier of medical science. We have introduced for the first time cyclopropenium-containing nanoparticles as a cationic carrier for gene transfection, as an alternative to common quaternary ammonium transfection agents. Cyclopropenium-based cationic nanoparticles were prepared by crosslinking poly(ethylene imine) (PEI) with tetrachlorocyclopropene. These nanoparticles were electrostatically complexed with plasmid DNA into polyplexes (~50 nm). Their cellular uptake into F929 mouse fibroblast cells, and their eventual expression in vitro were successfully confirmed. Cyclopropenium-based nanoparticles displayed enhanced transfection relative to PEI with minimal toxicity, which makes them novel and promising candidates for gene therapy.

Nanoparticles bearing cyclopropenium cation were prepared as biodegradable polymers that undergo hydrolytic degradation and swell significantly, displaying an important framework for the drug-delivery capabilities of a hydrolytically degradable cationic polyester. Antimicrobial effects were observed against Staphylococcus epidermidis, taking further advantage of cyclopropenium nanoparticles in a biological context.