CONICET | Buscador de Institutos y Recursos Humanos

Arginine-rich cell-penetrating peptides are known to be effectively internalized by cells due to positively charged guanidine groups on the structure. Inspired by arginine containing cell-penetrating peptides, arginine containing synthetic polymers potentially offers cell-penetrating ability along with a variety of enhanced properties such as stability, amphiphilicity stimuli-responsive and chemical functionality, which altogether may improve biological function.. Our group has designed and synthesized arginine-containing polymers via three different synthetic approaches for potential drug/gene delivery applications.. Post-polymerization modification approach involves modification of primary amine-reactive pentafluoromethacrylate polymers with arginine to obtain arginine methacrylate polymers as potential as siRNA delivery systems. These polymers were further modified with octaarginine residues for potential co-delivery of an anticancer drug and siRNA. In the second approach, an arginine containing methacrylate monomer, arginine methyl ester methacrylamide (AMME), was synthesized using arginine amino acid (i.e. arginine methyl ester) having unprotected guanidine group as a starting compound, and polymerized via RAFT polymerization to directly obtain well-defined polymers of arginine. The third approach,utilized an in-situ polymerization/ approach to yield cyclic RGD-end-functionalized well-defined polymers as potential building blocks of targeted drug delivery systems. Results demonstrated that while all synthesized ?polymers with pendant arginine residues could stably complex with siRNA at low N/P ratios due to electrostatic interactions through their positively charged guanidine groups and effectively cross cellular membranes, RGD-ended well-defined polymers were internalized distinctly by cancer and health cell lines