INVESTIGADORES
POLICASTRO Lucia Laura
congresos y reuniones científicas
Título:
Evaluation of a novel bioresorbable polyester as gene delivery carrier
Autor/es:
CARACCIOLO P; PARRA F; ABRAHAM G; VÁZQUEZ B; SAN ROMÁN J; POLICASTRO LL; PODHAJCER O
Lugar:
Natal
Reunión:
Congreso; 7th. Latin American Congress of Artificial Organs and Biomaterials; 2012
Resumen:
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 amino-group
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.