Evidence map›Paper›PMID 29653579›Full record

ArticleJournal of nanobiotechnology2018

Delivery of siRNA in vitro and in vivo using PEI-capped porous silicon nanoparticles to silence MRP1 and inhibit proliferation in glioblastoma.

Wing Yin Tong, Mohammed Alnakhli, Richa Bhardwaj, Sinoula Apostolou, Sougata Sinha, Cara Fraser, Tim Kuchel, Bryone Kuss, Nicolas H Voelcker

Open access · goldAbstract read
In one paragraph

Article in Journal of nanobiotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

30 citing papers in PubMed, 85 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. NonviralACS nano · 2023
    Article
  5. Article
  6. Review
  7. Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023
    Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Small Interfering RNA for Gliomas Treatment: Overcoming Hurdles in Delivery.Frontiers in cell and developmental biology · 2022
    Review
  18. Review
  19. Article
  20. 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 5 institutions in 1 country.

Wing Yin TongMonash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Mohammed AlnakhliSchool of Medicine, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia.
Richa BhardwajFuture Industries Institute, University of South Australia, Mawson Lakes, Adelaide, SA, 5095, Australia.
Sinoula ApostolouSchool of Medicine, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia.
Sougata SinhaFuture Industries Institute, University of South Australia, Mawson Lakes, Adelaide, SA, 5095, Australia.
Cara FraserSouth Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia.
Tim KuchelSouth Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia.
Bryone KussSchool of Medicine, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia. Bryone.Kuss@sa.gov.au.
Nicolas H VoelckerMonash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia. nicolas.voelcker@monash.edu.
Flinders University · AUSouth Australian Health and Medical Research Institute · AUUniversity of South Australia · AUAustralian National Fabrication Facility · AUMelbourne Centre for Nanofabrication · AU

Funding

Science and Industry Endowment Fund PF16-072
6 · The paper itself

Abstract

backgroundMultidrug resistance-associated protein 1 (MRP1) overexpression plays a major role in chemoresistance in glioblastoma multiforme (GBM) contributing to its notorious deadly nature. Although MRP1-siRNA transfection to GBM in vitro has been shown to sensitise the cells to drug, MRP1 silencing in vivo and the phenotypic influence on the tumour and normal tissues upon MRP1 down-regulation have not been established. Here, porous silicon nanoparticles (pSiNPs) that enable high-capacity loading and delivery of siRNA are applied in vitro and in vivo.

resultWe established pSiNPs with polyethyleneimine (PEI) capping that enables high-capacity loading of siRNA (92 µg of siRNA/mg PEI-pSiNPs), and optimised release profile (70% released between 24 and 48 h). These pSiNPs are biocompatible, and demonstrate cellular uptake and effective knockdown of MRP1 expression in GBM by 30%. Also, siRNA delivery was found to significantly reduce GBM proliferation as an associated effect. This effect is likely mediated by the attenuation of MRP1 transmembrane transport, followed by cell cycle arrest. MRP1 silencing in GBM tumour using MRP1-siRNA loaded pSiNPs was demonstrated in mice (82% reduction at the protein level 48 h post-injection), and it also produced antiproliferative effect in GBM by reducing the population of proliferative cells. These results indicate that in vitro observations are translatable in vivo. No histopathological signs of acute damage were observed in other MRP1-expressing organs despite collateral downregulations.

conclusionsThis study proposes the potential of efficient MRP1-siRNA delivery by using PEI-capped pSiNPs in achieving a dual therapeutic role of directly attenuating the growth of GBM while sensitising residual tumour cells to the effects of chemotherapy post-resection.

Indexed as

Gene SilencingAnimalsATP-Binding Cassette, Sub-Family C ProteinsCell Cycle CheckpointsCell Line, TumorCell ProliferationGene Knockdown TechniquesGlioblastomaHumansMice, NudeNanoparticlesOrgan SpecificityPhenotypePolyethyleneiminePorosityPropionatesATP-Binding Cassette, Sub-Family C Proteinsmultidrug resistance-associated protein 1PolyethyleneiminePropionatesQuinolinesRNA, Small InterferingSiliconverlukastBrain tumourCell proliferationGene deliveryMultidrug resistance-associated proteinNanoparticlessiRNA

Identifiers

PMID29653579
PMCPMC5898074
OpenAlexW2797089132

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.