Hydrolytically degrading nano-polyplexes (HDG-NPs) that reverse charge through conversion of tertiary amines to carboxylic acids were investigated to improve intracellular un-packaging of siRNA and target gene silencing compared to a non-degradable analog (non-HDG-NPs). Both NP types comprised reversible addition-fragmentation chain-transfer (RAFT) synthesized diblock copolymers of a poly(ethylene glycol) (PEG) corona-forming block and a cationic block for nucleic acid packaging that incorporated butyl methacrylate (BMA) and either dimethylaminoethyl methacrylate (DMAEMA, non-HDG-NPs) or dimethylaminoethyl acrylate (DMAEA, HDG-NPs). HDG-NPs decreased significantly in size and released significantly more siRNA (∼40%) than non-HDG-NPs after 24 h in aqueous solution. While both HDG-NPs and non-HDG-NPs had comparable uptake and cytotoxicity up to 150 nM siRNA doses, HDG-NPs achieved significantly higher target gene silencing of the model gene luciferase in vitro. High resolution FRET confocal microscopy was used to monitor the intracellular un-packaging of siRNA. Non-HDG-NPs had significantly higher FRET efficiency than HDG-NPs, indicating that siRNA delivered from HDG-NPs was more fully un-packaged and therefore had improved intracellular bioavailability.
Hydrolytin class="Chemical">cally degrading nanpan>o-polyplexes (HDG-NPs) that reverse charge through conversion of tertiary amines to carboxylic acids were investigated to improve intracellular un-packaging of siRNA and target gene silencing compared to a non-degradable analog (non-HDG-NPs). Both NP types comprised reversible addition-fragmentation chain-transfer (RAFT) synthesized diblock copolymers of a poly(ethylene glycol) (PEG) corona-forming block and a cationic block for nucleic acid packaging that incorporated butyl methacrylate (BMA) and either dimethylaminoethyl methacrylate (DMAEMA, non-HDG-NPs) or dimethylaminoethyl acrylate (DMAEA, HDG-NPs). HDG-NPs decreased significantly in size and released significantly more siRNA (∼40%) than non-HDG-NPs after 24 h in aqueous solution. While both HDG-NPs and non-HDG-NPs had comparable uptake and cytotoxicity up to 150 nM siRNA doses, HDG-NPs achieved significantly higher target gene silencing of the model gene luciferase in vitro. High resolution FRET confocal microscopy was used to monitor the intracellular un-packaging of siRNA. Non-HDG-NPs had significantly higher FRET efficiency than HDG-NPs, indicating that siRNA delivered from HDG-NPs was more fully un-packaged and therefore had improved intracellular bioavailability.
Authors: Nguyen T D Tran; Nghia P Truong; Wenyi Gu; Zhongfan Jia; Matthew A Cooper; Michael J Monteiro Journal: Biomacromolecules Date: 2013-01-16 Impact factor: 6.988
Authors: Broes Naeye; Hendrik Deschout; Vicky Caveliers; Benedicte Descamps; Kevin Braeckmans; Christian Vanhove; Jo Demeester; Tony Lahoutte; Stefaan C De Smedt; Koen Raemdonck Journal: Biomaterials Date: 2012-12-20 Impact factor: 12.479
Authors: Jürgen Soutschek; Akin Akinc; Birgit Bramlage; Klaus Charisse; Rainer Constien; Mary Donoghue; Sayda Elbashir; Anke Geick; Philipp Hadwiger; Jens Harborth; Matthias John; Venkitasamy Kesavan; Gary Lavine; Rajendra K Pandey; Timothy Racie; Kallanthottathil G Rajeev; Ingo Röhl; Ivanka Toudjarska; Gang Wang; Silvio Wuschko; David Bumcrot; Victor Koteliansky; Stefan Limmer; Muthiah Manoharan; Hans-Peter Vornlocher Journal: Nature Date: 2004-11-11 Impact factor: 49.962
Authors: Mark E Davis; Jonathan E Zuckerman; Chung Hang J Choi; David Seligson; Anthony Tolcher; Christopher A Alabi; Yun Yen; Jeremy D Heidel; Antoni Ribas Journal: Nature Date: 2010-03-21 Impact factor: 49.962
Authors: Hongmei Li; Martina Miteva; Kellye C Kirkbride; Ming J Cheng; Christopher E Nelson; Elaine M Simpson; Mukesh K Gupta; Craig L Duvall; Todd D Giorgio Journal: Biomacromolecules Date: 2014-12-19 Impact factor: 6.988
Authors: Makan Khoshnejad; Colin F Greineder; Katherine W Pulsipher; Carlos H Villa; Burcin Altun; Daniel C Pan; Andrew Tsourkas; Ivan J Dmochowski; Vladimir R Muzykantov Journal: Bioconjug Chem Date: 2018-02-19 Impact factor: 4.774
Authors: Samantha M Sarett; Thomas A Werfel; Irene Chandra; Meredith A Jackson; Taylor E Kavanaugh; Madison E Hattaway; Todd D Giorgio; Craig L Duvall Journal: Biomaterials Date: 2016-04-21 Impact factor: 12.479
Authors: Evan B Glass; Shirin Masjedi; Stephanie O Dudzinski; Andrew J Wilson; Craig L Duvall; Fiona E Yull; Todd D Giorgio Journal: ACS Omega Date: 2019-10-01