Evidence map›Paper›PMID 25204289›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2014

Decationized polyplexes as stable and safe carrier systems for improved biodistribution in systemic gene therapy.

Luís Novo, Larissa Y Rizzo, Susanne K Golombek, George R Dakwar, Bo Lou, Katrien Remaut, Enrico Mastrobattista, Cornelus F van Nostrum, Wilhelm Jahnen-Dechent, Fabian Kiessling and 3 more

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Charge-Conversion Strategies for Nucleic Acid Delivery.Advanced functional materials · 2021
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Rod-Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2017
    Article
  10. Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 3 countries.

Luís Novo *Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Larissa Y Rizzo *Nanomedicines and Theranostics, Department for Experimental Molecular Imaging, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Susanne K GolombekNanomedicines and Theranostics, Department for Experimental Molecular Imaging, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
George R DakwarLaboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent Research Group on Nanomedicines, Harelbekestraat 72, 9000 Ghent, Belgium.
Bo LouDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Katrien RemautLaboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent Research Group on Nanomedicines, Harelbekestraat 72, 9000 Ghent, Belgium.
Enrico MastrobattistaDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Cornelus F van NostrumDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Wilhelm Jahnen-DechentHelmholtz Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University, Aachen, Germany.
Fabian KiesslingNanomedicines and Theranostics, Department for Experimental Molecular Imaging, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Kevin BraeckmansLaboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent Research Group on Nanomedicines, Harelbekestraat 72, 9000 Ghent, Belgium.
Twan LammersDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Wim E HenninkDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Utrecht University · NLRWTH Aachen University · DEGhent University · BE

Funding

European Research Council 309495
6 · The paper itself

Abstract

Many polycation-based gene delivery vectors show high transfection in vitro, but their cationic nature generally leads to significant toxicity and poor in vivo performance which significantly hampers their clinical applicability. Unlike conventional polycation-based systems, decationized polyplexes are based on hydrophilic and neutral polymers. They are obtained by a 3-step process: charge-driven condensation followed by disulfide crosslinking stabilization and finally polyplex decationization. They consist of a disulfide-crosslinked poly(hydroxypropyl methacrylamide) (pHPMA) core stably entrapping plasmid DNA (pDNA), surrounded by a shell of poly(ethylene glycol) (PEG). In the present paper the applicability of decationized polyplexes for systemic administration was evaluated. Cy5-labeled decationized polyplexes were evaluated for stability in plasma by fluorescence single particle tracking (fSPT), which technique showed stable size distribution for 48 h unlike its cationic counterpart. Upon the incubation of the polymers used for the formation of polyplexes with HUVEC cells, MTT assay showed excellent cytocompatibility of the neutral polymers. The safety was further demonstrated by a remarkable low teratogenicity and mortality activity of the polymers in a zebrafish assay, in great contrast with their cationic counterpart. Near infrared (NIR) dye-labeled polyplexes were evaluated for biodistribution and tumor accumulation by noninvasive optical imaging when administered systemically in tumor bearing mice. Decationized polyplexes exhibited an increased circulation time and higher tumor accumulation, when compared to their cationic precursors. Histology of tumors sections showed that decationized polyplexes induced reporter transgene expression in vivo. In conclusion, decationized polyplexes are a platform for safer polymeric vectors with improved biodistribution properties when systemically administered.

Indexed as

Gene Transfer TechniquesAnimalsCell Line, TumorCell SurvivalDNADrug StabilityEmbryo, NonmammalianFemaleGreen Fluorescent ProteinsHumansHuman Umbilical Vein Endothelial CellsMice, NudeNeoplasmsParticle SizePlasmidsPolymersDNAenhanced green fluorescent proteinGreen Fluorescent ProteinsPolymersBiocompatibilityBiodistributionEPRGene deliveryNanoparticlePolymer

Identifiers

PMID25204289
PMCPMC4254847
OpenAlexW2120486710

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.