Evidence map›Paper›PMID 29899810›Full record

ArticleCancer nanotechnology2018

Gene therapy with RALA/iNOS composite nanoparticles significantly enhances survival in a model of metastatic prostate cancer.

Cian M McCrudden, John W McBride, Joanne McCaffrey, Emma M McErlean, Nicholas J Dunne, Vicky L Kett, Jonathan A Coulter, Tracy Robson, Helen O McCarthy

Open access · goldAbstract read
In one paragraph

Article in Cancer nanotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

13 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  8. Nucleic acid vaccination strategies for ovarian cancer.Frontiers in bioengineering and biotechnology · 2022
    Review
  9. Review
  10. Article
  11. Peptide-Assisted Nucleic Acid Delivery Systems on the Rise.International journal of molecular sciences · 2021
    Review
  12. Review
  13. Review
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

9 authors at 3 institutions in 2 countries.

Cian M McCrudden1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.
John W McBride1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.
Joanne McCaffrey1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.
Emma M McErlean1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.
Nicholas J Dunne2School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin, Ireland.
Vicky L Kett1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.
Jonathan A Coulter1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.
Tracy Robson3Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
Helen O McCarthy1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.ORCID 0000-0002-1254-3745
Queen's University Belfast · GBDublin City University · IERoyal College of Surgeons in Ireland · IE

Funding

Cancer Research UK 18475Cancer Research UK A14271Medical Research Council G1001473
6 · The paper itself

Abstract

backgroundRecent approvals of gene therapies by the FDA and the EMA for treatment of inherited disorders have further opened the door for assessment of nucleic acid pharmaceuticals for clinical usage. Arising from the presence of damaged or inappropriate DNA, cancer is a condition particularly suitable for genetic intervention. The RALA peptide has been shown to be a potent non-viral delivery platform for nucleic acids. This study examines the use of RALA to deliver a plasmid encoding inducible nitric oxide synthase (iNOS) as an anti-cancer treatment.

methodsThe physiochemical properties of the RALA/DNA nanoparticles were characterized via dynamic light scattering and transmission electron microscopy. The nanoparticles were labelled with fluorophores and tracked over time using confocal microscopy with orthogonal sections to determine cellular location. In vitro studies were employed to determine functionality of the nanoparticles both for pEGFP-N1 and CMV-iNOS. Nanoparticles were injected intravenously into C57/BL6 mice with blood and serum samples analysed for immune response. PC3-luc2M cells were injected into the left ventricle of SCID mice followed by treatment with RALA/CMV-iNOS nanoparticles to evaluate the tumour response in a metastatic model of prostate cancer.

resultsFunctional cationic nanoparticles were produced with gene expression in PC-3 prostate cancer cells. Furthermore, repeated administrations of RALA/DNA nanoparticles into immunocompetent mice did not produce any immunological response: neutralization of the vector or release of inflammatory mediators. RALA/CMV-iNOS reduced the clonogenicity of PC-3 cells in vitro, and in an in vivo model of prostate cancer metastasis, systemically delivered RALA/CMV-iNOS significantly improved the survival of mice.

conclusionThese studies further validate RALA as a genetic cargo delivery vehicle and iNOS as a potent therapy for the treatment of cancer.

Indexed as

Amphipathic peptideiNOSNitric oxideNon-viral gene therapyProstate cancer

Identifiers

PMID29899810
PMCPMC5982451
OpenAlexW2794138048

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.