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Amino Acid-Functionalized Dendritic Polyglycerol For Safe And Effective SiRNA Delivery.
Hanxiang Zeng, Cathleen Schlesener, Olivia R. Cromwell, M. Hellmund, R. Haag, Zhibin Guan
Published 2015 · Chemistry, Medicine
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The development of safe and effective delivery vectors is a great challenge for the medicinal application of RNA interference (RNAi). In this study, we aimed to develop new synthetic transfection agents based on dendritic polyglycercol (dPG), which has shown great biocompatibility in several biomaterial applications. Histidine and aromatic amino acids were conjugated to the amine-terminated dPGs through amide bonds. We systematically tuned the amino acid combination, functionalization ratio, ligand density, and dPG core size to find optimal vectors. It was found that histidine-tryptophan-functionalized dPGs exhibited improved delivery efficiency and greatly reduced toxicity over simple amine-terminated dPGs. Furthermore, the optimized vectors exhibited strong siRNA binding and high transfection efficiency in serum containing media. The results indicate that the current amino acid-functionalized dPG system is a promising candidate for in vivo siRNA delivery applications.
This paper references
Dendritic polyglycerols with oligoamine shells show low toxicity and high siRNA transfection efficiency in vitro.
W. Fischer (2010)
Dendrimers and dendrons for siRNA binding: computational insights
G. M. Pavan (2012)
RNA Interference: Biology, Mechanism, and Applications
N. Agrawal (2003)
siRNA as a conventional drug in the clinic? Challenges and current technologies.
M. Shim (2012)
Systematic adjustment of charge densities and size of polyglycerol amines reduces cytotoxic effects and enhances cellular uptake.
M. Hellmund (2015)
Membrane activity and transfection ability of amphipathic polycations as a function of alkyl group size.
D. Wakefield (2005)
Multifunctional dendronized peptide polymer platform for safe and effective siRNA delivery.
Hanxiang Zeng (2013)
Inhibition of influenza virus infection by multivalent sialic-acid-functionalized gold nanoparticles.
Ilona Papp (2010)
RNA Interference in Biology and Medicine
O. Milhavet (2003)
Polyglycerol coatings of glass vials for protein resistance.
Kerstin Hoeger (2013)
Toxicity of cationic lipids and cationic polymers in gene delivery.
Hongtao Lv (2006)
The promises and pitfalls of RNA-interference-based therapeutics
D. Castanotto (2009)
Controlled synthesis of cell-laden microgels by radical-free gelation in droplet microfluidics.
Torsten Rossow (2012)
Inhibition of Influenza Virus Activity by Multivalent Glycoarchitectures with Matched Sizes
Ilona Papp (2011)
Drug Discovery Today: Technologies (2007) volume 4 issues 3/4.
S. Carney (2007)
2013 FDA drug approvals
A. Mullard (2014)
In vivo delivery of small interfering RNA to tumors and their vasculature by novel dendritic nanocarriers
P. Ofek (2010)
Synthesis and biological evaluation of radio and dye labeled amino functionalized dendritic polyglycerol sulfates as multivalent anti-inflammatory compounds.
D. Gröger (2013)
Comparison of the endocytic properties of linear and branched PEIs, and cationic PAMAM dendrimers in B16f10 melanoma cells.
F. P. Seib (2007)
Does tryptophan intercalate in DNA? A comparative study of peptide binding to alternating and nonalternating A.T sequences.
M. Rajeswari (1987)
Dendritic polyglycerol: a new versatile biocompatible-material.
H. Frey (2002)
A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells.
L. Crombez (2009)
Targeted delivery of dendritic polyglycerol-doxorubicin conjugates by scFv-SNAP fusion protein suppresses EGFR+ cancer cell growth.
Ahmad Fawzi Hussain (2013)
Structure-Based Design of Dendritic Peptide Bolaamphiphiles for siRNA Delivery
Hanxiang Zeng (2015)
Nucleic acid delivery: the missing pieces of the puzzle?
J. Nguyen (2012)
Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection
Fatemeh Sheikhi Mehrabadi (2015)
Elucidating the molecular mechanism of PAMAM-siRNA dendriplex self-assembly: effect of dendrimer charge density.
L. B. Jensen (2011)
The role of macromolecular architecture in passively targeted polymeric carriers for drug and gene delivery
S. Grayson (2008)
Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation
J. Dernedde (2010)
Delivery materials for siRNA therapeutics.
R. Kanasty (2013)
Multivalency as a chemical organization and action principle.
Carlo Fasting (2012)
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Huan Peng (2016)
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Yuxin Han (2016)
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S. Song (2016)