Peptide-Based Star Polymers as Potential siRNA Carriers*
Shu Jie Lam A , Adrian Sulistio A , Katharina Ladewig A , Edgar H. H. Wong A , Anton Blencowe A B C and Greg G. Qiao A CA Polymer Science Group, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Vic. 3010, Australia.
B Current address: Mawson Institute, Division of Information Technology, Engineering and the Environment, University of South Australia, Mawson Lakes, SA 5095, Australia.
C Corresponding authors. Email: anton.blencowe@unisa.edu.au; gregghq@unimelb.edu.au
Australian Journal of Chemistry 67(4) 592-597 https://doi.org/10.1071/CH13525
Submitted: 30 September 2013 Accepted: 21 October 2013 Published: 19 November 2013
Abstract
16- and 32-arm star polymers were synthesised using poly(amido amine) (PAMAM) dendrimers as multifunctional initiators for the ring-opening polymerisation (ROP) of ϵ-Z-l-lysine N-carboxyanhydride (Lys NCA) via the core-first approach. The resulting star polymers were subsequently post-functionalised with poly(ethylene glycol) (PEG) via carbodiimide coupling, potentially improving the biodistribution of the stars in vivo. De-protection of the carboxybenzyl (Cbz)-protected star arms yielded water-soluble cationic poly(l-lysine) (PLL) star polymers with hydrodynamic radii ranging from 2.0 to 3.3 nm. Successful complexation of the PLL star polymers with double-stranded oligodeoxynucleotides (ODNs)—a mimic for small interfering RNA (siRNA)—was achieved at a nitrogen-to-phosphate (N/P) ratio of 5. Cell viability studies using HEK293T cells indicated the ‘safe’ concentration for these polymers is within a suitable window for the delivery of siRNA therapeutics.
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