Evidence map›Paper›PMID 22686936›Full record

ArticleMolecular pharmaceutics2012

Nanoparticle delivery of pooled siRNA for effective treatment of non-small cell lung cancer.

Yang Yang, Yunxia Hu, Yuhua Wang, Jun Li, Feng Liu, Leaf Huang

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

35 citing papers in PubMed, 86 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Exosomal targeting and its potential clinical application.Drug delivery and translational research · 2022
    Review
  6. Review
  7. Article
  8. Review
  9. Anti-Biomedicines · 2020
    Review
  10. Article
  11. Cancer-Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery.Advanced materials (Deerfield Beach, Fla.) · 2020
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Lipid Nanovectors to Deliver RNA Oligonucleotides in Cancer.Nanomaterials (Basel, Switzerland) · 2016
    Review
  19. Review
  20. 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

6 authors at 1 institution in 1 country.

Yang YangDivision of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Yunxia Hu
Yuhua Wang
Jun Li
Feng Liu
Leaf Huang
University of North Carolina at Chapel Hill · US

Funding

Translational Nanosystems for Improved Lung Cancer Treatment with Small MoleculesU54CA151652 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAROON, ZISHAN A, TEPPER, JOEL E · 2010 to 2014
$12.1M
LPD Nanoparticles in Anti-Cancer TherapyR01CA129835 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HUANG, LEAF · 2008 to 2012
$1.5M
Novel nanoparticles for siRNA deliveryR01CA149363 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HUANG, LEAF · 2010 to 2014
$1.3M
NCI NIH HHS CA129835NCI NIH HHS CA149363NCI NIH HHS CA151652NCI NIH HHS R01 CA129835NCI NIH HHS R01 CA149363NCI NIH HHS U54 CA151652
6 · The paper itself

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. To explore the potential of small interfering RNA (siRNA) therapy for NSCLC, we have developed anisamide-targeted LCP to efficiently deliver siRNA into the cytoplasm of sigma receptor-expressing NSCLC cells. Targeted LCP demonstrated a 9-fold higher siRNA delivery efficiency compared to nontargeted LCP in A549 cells in vitro. To simultaneously target multiple oncogenic mechanisms, we coformulated three siRNA sequences targeting HDM2, c-myc and VEGF oncogenes, and investigated their efficacy of cell-killing in A549 and H460 cells in vitro. The results indicated that the pooled siRNA codelivered by the targeted LCP could effectively and simultaneously knock down HDM2, c-myc and VEGF expressions and significantly inhibit tumor cell growth. After iv injection of mice bearing A549 xenografted tumor with Texas Red-labeled siRNA formulated in the targeted LCP, siRNA was successfully delivered to and concentrated in the tumor cells. Repeated intravenous injections of mice with pooled siRNA formulated in the targeted LCP significantly impaired NSCLC growth in vivo (p < 0.01) for both A549 and H460 tumors, demonstrating an ED50 for the treatment of ∼ 0.2 mg/kg in A549 tumors. The enhanced antitumor activity is due to the fact that the silencing of HDM2/c-myc/VEGF could inhibit tumor proliferation and angiogenesis and also simultaneously induce tumor apoptosis. Our results demonstrate that the targeted LCP is a promising vector to deliver pooled siRNA into tumors and to achieve multiple target blocking. This is potentially a valid therapeutic modality in the gene therapy of human NSCLC.

Indexed as

AnimalsApoptosisCarcinoma, Non-Small-Cell LungCell Line, TumorCell SurvivalFemaleFlow CytometryGenes, mycHumansMiceMice, NudeNanoparticlesProto-Oncogene Proteins c-mdm2Reverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingVascular Endothelial Growth Factor AMDM2 protein, humanProto-Oncogene Proteins c-mdm2RNA, Small InterferingVascular Endothelial Growth Factor A

Identifiers

PMID22686936
PMCPMC3484223
OpenAlexW2076754526

What OpenQuestion holds

Textmetadata
LicenceTDM
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.