CONICET | Buscador de Institutos y Recursos Humanos

In the last decades, gene therapy has gained attention due to its potential to treat chronic diseases and genetic disorders, in addition to cancer and infectious diseases such as AIDS. Cationic polymers can potentially complex DNA, not only protecting it from nuclease degradation, but also generating polyplexes with a nanoscale size small enough to enter the cell through endocytosis. Polycations can provide a pH-buffering ability allowing them to behave as proton sponges, assisting the escape of complexes from endosome and potentially improving the transfection efficiency. In this work, a bioresorbable polymer potentially suitable for DNA complexation and gene delivery was synthesized and studied as gene delivery carrier. A polyester based on tetraethylene glycol (TEG) and L-glutamic acid was synthesized from piro L-glutamic acid (pGlu) by aminogroup protection with di-tert-butyl dicarbonate. After deprotection, the amino moieties were available to interact with DNA. Number average molecular weight of the polyester resulted 2430 Da, with a polydispersity of 1.4. The material displayed a pKa of 6.8, which lays between cytosomal and endosomal pH. This result indicates that the buffering capacity of the cationic polymer could facilitate endosomal escape of polymer-DNA polyplexes by osmolysis. The polyester showed complexation capacity towards pGL3-Promoter plasmid after assaying different polymer/DNA ratios. Moreover, several concentrations of the polyplexes were tested against colorectal cancer cells, displaying no cytotoxicity. The polyplexes, however, were not able to transfect cells, maybe due to the low molecular weight of the polycation. In this direction, polyesters with the same backbone and higher molecular weights are currently being synthesized to assess their transfection efficiency.