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Structural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles in siRNA delivery

The multiformity in polymer structure and conformation design provides a great potential in improving the gene silencing efficiency of siRNA by polymer vectors. In order to provide information on the polymer design for siRNA delivery, the structural contributions of blocked or grafted poly(2-dimethy... Full description

Journal Title: Biomaterials 2011, Vol.32(33), pp.8730-8742
Main Author: Lin, Daoshu
Other Authors: Huang, Yuanyu , Jiang, Qian , Zhang, Wendi , Yue, Xinye , Guo, Shutao , Xiao, Ping , Du, Quan , Xing, Jinfeng , Deng, Liandong , Liang, Zicai , Dong, Anjie
Format: Electronic Article Electronic Article
Language: English
Subjects:
Peg
ID: ISSN: 0142-9612 ; E-ISSN: 1878-5905 ; DOI: 10.1016/j.biomaterials.2011.07.089
Link: https://www.sciencedirect.com/science/article/pii/S0142961211008866
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recordid: elsevier_sdoi_10_1016_j_biomaterials_2011_07_089
title: Structural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles in siRNA delivery
format: Article
creator:
  • Lin, Daoshu
  • Huang, Yuanyu
  • Jiang, Qian
  • Zhang, Wendi
  • Yue, Xinye
  • Guo, Shutao
  • Xiao, Ping
  • Du, Quan
  • Xing, Jinfeng
  • Deng, Liandong
  • Liang, Zicai
  • Dong, Anjie
subjects:
  • Non-Viral Carriers
  • Pdmaema
  • Peg
  • Sirna Delivery
  • Cationic Polymer Nanoparticles
  • Medicine
  • Engineering
ispartof: Biomaterials, 2011, Vol.32(33), pp.8730-8742
description: The multiformity in polymer structure and conformation design provides a great potential in improving the gene silencing efficiency of siRNA by polymer vectors. In order to provide information on the polymer design for siRNA delivery, the structural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles (NPs) in siRNA delivery were studied. Herein, two kinds of self-assembly nanoparticles (NPs) formed by amphiphilic cationic polymers, methoxy poly(ethylene glycol)-block-polycaprolactone-block-poly(2-dimethylaminoethyl methacrylate) (mPEG-PCL- -PDMAEMA, PEC D) and methoxy poly(ethylene glycol)-block-(polycaprolactone-graft-poly(2-dimethylaminoethyl methacrylate)) (mPEG-PCL- -PDMAEMA, PEC D), were used to deliver siRNA for and studies. The physiochemical properties including size and zeta potential of PEC D NPs/siRNA and PEC D NPs/siRNA complexes were characterized. cytotoxicity, cellular uptake and siRNA knockdown efficiency were evaluated in HeLa-Luc cells. The endosome escape and intracellular distribution of PEC D NPs/siRNA and PEC D NPs/siRNA in HeLa-Luc cells were also observed. polymer mediated siRNA delivery and the complexes distribution in isolated organs were studied using mice and tumor-bearing mice. At the same total degree of polymerization (DP) of DMAEMA, PEC D NPs/siRNA complexes possessed higher zeta potentials than PEC D NPs/siRNA complexes (at the same N/P ratio), which may be the reason that PEC D NPs/siRNA complexes can deliver more siRNA into the cytoplasm and lead to higher luciferase and lamin A/C silencing efficiency than PEC D NPs/siRNA complexes. The imaging measurement and histochemical analysis also confirmed that siRNA could be delivered to lungs, livers, pancreas and HeLa-Luc tumors more efficiently by PEC D NPs than PEC D NPs. Meanwhile, the PDMAEMA chains of PEC D could be shortened which provides benefits for clearing. Therefore, PEC D NPs have great potential to be used as efficient non-viral carriers for siRNA delivery.
language: eng
source:
identifier: ISSN: 0142-9612 ; E-ISSN: 1878-5905 ; DOI: 10.1016/j.biomaterials.2011.07.089
fulltext: fulltext
issn:
  • 0142-9612
  • 01429612
  • 1878-5905
  • 18785905
url: Link


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titleStructural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles in siRNA delivery
creatorLin, Daoshu ; Huang, Yuanyu ; Jiang, Qian ; Zhang, Wendi ; Yue, Xinye ; Guo, Shutao ; Xiao, Ping ; Du, Quan ; Xing, Jinfeng ; Deng, Liandong ; Liang, Zicai ; Dong, Anjie
ispartofBiomaterials, 2011, Vol.32(33), pp.8730-8742
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subjectNon-Viral Carriers ; Pdmaema ; Peg ; Sirna Delivery ; Cationic Polymer Nanoparticles ; Medicine ; Engineering
descriptionThe multiformity in polymer structure and conformation design provides a great potential in improving the gene silencing efficiency of siRNA by polymer vectors. In order to provide information on the polymer design for siRNA delivery, the structural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles (NPs) in siRNA delivery were studied. Herein, two kinds of self-assembly nanoparticles (NPs) formed by amphiphilic cationic polymers, methoxy poly(ethylene glycol)-block-polycaprolactone-block-poly(2-dimethylaminoethyl methacrylate) (mPEG-PCL- -PDMAEMA, PEC D) and methoxy poly(ethylene glycol)-block-(polycaprolactone-graft-poly(2-dimethylaminoethyl methacrylate)) (mPEG-PCL- -PDMAEMA, PEC D), were used to deliver siRNA for and studies. The physiochemical properties including size and zeta potential of PEC D NPs/siRNA and PEC D NPs/siRNA complexes were characterized. cytotoxicity, cellular uptake and siRNA knockdown efficiency were evaluated in HeLa-Luc cells. The endosome escape and intracellular distribution of PEC D NPs/siRNA and PEC D NPs/siRNA in HeLa-Luc cells were also observed. polymer mediated siRNA delivery and the complexes distribution in isolated organs were studied using mice and tumor-bearing mice. At the same total degree of polymerization (DP) of DMAEMA, PEC D NPs/siRNA complexes possessed higher zeta potentials than PEC D NPs/siRNA complexes (at the same N/P ratio), which may be the reason that PEC D NPs/siRNA complexes can deliver more siRNA into the cytoplasm and lead to higher luciferase and lamin A/C silencing efficiency than PEC D NPs/siRNA complexes. The imaging measurement and histochemical analysis also confirmed that siRNA could be delivered to lungs, livers, pancreas and HeLa-Luc tumors more efficiently by PEC D NPs than PEC D NPs. Meanwhile, the PDMAEMA chains of PEC D could be shortened which provides benefits for clearing. Therefore, PEC D NPs have great potential to be used as efficient non-viral carriers for siRNA delivery.
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