ArticlePharmaceutical research2008
An acid sensitive ketal-based polyethylene glycol-oligoethylenimine copolymer mediates improved transfection efficiency at reduced toxicity.
Article in Pharmaceutical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 69 citations in OpenAlex.
- Dynamic carriers for therapeutic RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stimuli-Responsive Nanotechnology for RNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Bioreducible polycations as shuttles for therapeutic nucleic acid and protein transfection.Antioxidants & redox signaling · 2014Review
- A pH and redox dual responsive 4-arm poly(ethylene glycol)-block-poly(disulfide histamine) copolymer for non-viral gene transfection in vitro and in vivo.International journal of molecular sciences · 2014Article
- Current progress in gene delivery technology based on chemical methods and nano-carriers.Theranostics · 2014Review
- Crosslinked linear polyethylenimine enhances delivery of DNA to the cytoplasm.Journal of controlled release : official journal of the Controlled Release Society · 2013Article
- Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors.International journal of nanomedicine · 2013Article
- Poly[(ethylene oxide)-co-(methylene ethylene oxide)]: A hydrolytically-degradable poly(ethylene oxide) platform.ACS macro letters · 2012Article
- Zinc Finger Nucleases: Tailor-made for Gene Therapy.Drugs of the future · 2012Article
- Advances in polymeric and inorganic vectors for nonviral nucleic acid delivery.Therapeutic delivery · 2011Review
- Dendrimeric alkylated polyethylenimine nano-carriers with acid-cleavable outer cationic shells mediate improved transfection efficiency without increasing toxicity.Pharmaceutical research · 2010Article
- The silent (R)evolution of polymeric nucleic acid therapeutics.Pharmaceutical research · 2008Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDynamic PEG-polycation copolymers that release PEG and degrade into small fragments after cell entry might present efficient and biocompatible gene carriers.
methodsPEG-OEI-MK was synthesized by copolymerization of 5 kDa polyethyleneglycol (PEG) and 800 Da oligoethylenimines through acid-degradable acetone-bis-(N-maleimidoethyl)ketal linkers (MK). To evaluate any benefit of the reversible over stable linkage, also the corresponding pH-stable analog, PEG-OEI-BM, was synthesized via ether linkages. Luciferase and GFP expression plasmids were used for transfections, in vivo biocompatibility was evaluated by intravenous application of polymers in Balb/c mice.
resultsPEG-OEI-MK showed efficient DNA binding as analyzed by ethidium bromide exclusion, resulting in formation of polyplexes with sizes around 100 nm and surface charges of below 5 mV zeta potential. This surface shielding of PEG-OEI-MK polyplexes remained stable at neutral pH 7.4, while polyplexes deshielded and aggregated at pH 5 within 15-30 min. Cell culture experiments demonstrated reduced polymer toxicity compared to the non-PEGylated OEI-MK. Transfection experiments demonstrated reduced gene expression of PEG-OEI-BM compared with the non-PEGylated analog OEI-BM, whereas the pH-reversible polymer PEG-OEI-MK mediated a significant increased transfection efficiency over the non-PEGylated OEI-MK.
conclusionsPEG-OEI-MK mediated the highest gene transfer at lowest cytotoxicity levels and also best in vivo biocompatibility.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.