Peptide-based star polymers as potential siRNA carriers

Shu Jie Lam; Adrian Sulistio; Katharina Ladewig; Edgar Hoe Hon Wong; Anton Blencowe; Greg Qiao

doi:10.1071/CH13525

Peptide-based star polymers as potential siRNA carriers

Shu Jie Lam, Adrian Sulistio, Katharina Ladewig, Edgar Hoe Hon Wong, Anton Blencowe, Greg Qiao

Research output: Contribution to journal › Article › Research › peer-review

25 Citations (Scopus)

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 3.3nm. 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.

Original language	English
Pages (from-to)	592-597
Number of pages	6
Journal	Australian Journal of Chemistry
Volume	67
Issue number	4
DOIs	https://doi.org/10.1071/CH13525
Publication status	Published - 2014
Externally published	Yes

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title = "Peptide-based star polymers as potential siRNA carriers",

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 3.3nm. 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.",

author = "Lam, {Shu Jie} and Adrian Sulistio and Katharina Ladewig and Wong, {Edgar Hoe Hon} and Anton Blencowe and Greg Qiao",

year = "2014",

doi = "10.1071/CH13525",

language = "English",

volume = "67",

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journal = "Australian Journal of Chemistry",

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T1 - Peptide-based star polymers as potential siRNA carriers

AU - Lam, Shu Jie

AU - Sulistio, Adrian

AU - Ladewig, Katharina

AU - Wong, Edgar Hoe Hon

AU - Blencowe, Anton

AU - Qiao, Greg

PY - 2014

Y1 - 2014

N2 - 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 3.3nm. 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.

AB - 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 3.3nm. 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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DO - 10.1071/CH13525

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AN - SCOPUS:84898483010

SN - 0004-9425

VL - 67

SP - 592

EP - 597

JO - Australian Journal of Chemistry

JF - Australian Journal of Chemistry

IS - 4

ER -

Peptide-based star polymers as potential siRNA carriers

Abstract

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