PMID- 21413702
OWN - NLM
STAT- MEDLINE
DCOM- 20110909
LR  - 20110509
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 12
IP  - 5
DP  - 2011 May 9
TI  - Hydrophilic cationic star homopolymers based on a novel diethanol-N-methylamine 
      dimethacrylate cross-linker for siRNA transfection: synthesis, characterization, 
      and evaluation.
PG  - 1468-79
LID - 10.1021/bm1014014 [doi]
AB  - Four cationic hydrophilic star homopolymers based on the novel hydrophilic, 
      positively ionizable cross-linker bis(methacryloyloxyethyl)methylamine (BMEMA) 
      were synthesized using sequential group transfer polymerization (GTP) and were, 
      subsequently, evaluated for their ability to deliver siRNA to mouse myoblast 
      cells. The nominal degrees of polymerization (DP) of the arms were varied from 10 
      to 50. For the polymerizations, 2-(dimethylamino)ethyl methacrylate (DMAEMA) was 
      employed as the hydrophilic, positively ionizable monomer. For comparison, four 
      linear DMAEMA homopolymers were also synthesized, whose nominal DPs were the same 
      as those of the arms of the stars. The numbers of arms of the star homopolymers 
      were determined using gel permeation chromatography with static light scattering 
      detection, and found to range from 7 to 19, whereas the hydrodynamic diameters of 
      the star homopolymers in aqueous solution were measured using dynamic light 
      scattering and found to increase with the arm DP from 13 to 26 nm. The presence 
      of the hydrophilic BMEMA cross-linker enabled the solubility of all star 
      homopolymers in pure water. The cloud points of the star homopolymers in aqueous 
      solution increased with the arm DP from 23 to 29  degrees C, while the cloud points of 
      the linear homopolymers were found to decrease with their DP, from 42 to 32  degrees C. 
      The effective pK values of the DMAEMA units were in the range of 6.9 to 7.3 for 
      the star homopolymers, whereas they ranged between 7.3 and 7.4 for the linear 
      homopolymers. Subsequently, all star and linear homopolymers were evaluated for 
      their ability to deliver siRNA to the C2C12 mouse myoblast cell line, expressing 
      the reporter enhanced green fluorescent protein (EGFP). All star homopolymers and 
      the largest linear homopolymer presented significant EGFP suppression, whereas 
      the smaller linear homopolymers were much less efficient. For all star 
      homopolymers and the largest linear homopolymer both the EGFP suppression and the 
      cell toxicity increased with polymer loading. The siRNA-specific EGFP 
      suppression, calculated by subtracting the effect of cell toxicity on EGFP 
      suppression, slightly increased with star polymer loading for the two smaller 
      stars, whereas it presented a shallow maximum and a decrease for the other two 
      stars. Moreover, the siRNA-specific EGFP suppression also increased slightly with 
      the DP of the arms of the DMAEMA star homopolymers. Overall, the EGFP suppression 
      efficiencies with the present star homopolymers were at levels comparable to that 
      of the commercially available transfection reagent Lipofectamine.
FAU - Pafiti, Kyriaki S
AU  - Pafiti KS
AD  - Department of Chemistry, University of Cyprus, Nicosia, Cyprus.
FAU - Mastroyiannopoulos, Nikolaos P
AU  - Mastroyiannopoulos NP
FAU - Phylactou, Leonidas A
AU  - Phylactou LA
FAU - Patrickios, Costas S
AU  - Patrickios CS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110317
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Cations)
RN  - 0 (Methacrylates)
RN  - 0 (Methylamines)
RN  - 0 (Polymers)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (bis(methacryloyloxyethyl)methylamine)
SB  - IM
MH  - *Cations
MH  - Magnetic Resonance Spectroscopy
MH  - Methacrylates/*chemistry
MH  - Methylamines/*chemistry
MH  - Polymers/*chemistry
MH  - RNA, Small Interfering/*genetics
MH  - *Transfection
EDAT- 2011/03/19 06:00
MHDA- 2011/09/10 06:00
CRDT- 2011/03/19 06:00
PHST- 2011/03/19 06:00 [entrez]
PHST- 2011/03/19 06:00 [pubmed]
PHST- 2011/09/10 06:00 [medline]
AID - 10.1021/bm1014014 [doi]
PST - ppublish
SO  - Biomacromolecules. 2011 May 9;12(5):1468-79. doi: 10.1021/bm1014014. Epub 2011 
      Mar 17.