Evidence map›Paper›PMID 25020033›Full record

ArticleMolecular pharmaceutics2014

Multifunctional cationic lipid-based nanoparticles facilitate endosomal escape and reduction-triggered cytosolic siRNA release.

Maneesh Gujrati, Anthony Malamas, Tesia Shin, Erlei Jin, Yunlu Sun, Zheng-Rong Lu

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
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

63 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Current gene therapy · 2025
    Article
  9. Review
  10. Review
  11. Review
  12. Emerging Cationic Nanovaccines.Pharmaceutics · 2024
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

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.

Maneesh GujratiDepartment of Biomedical Engineering, Case Western Reserve University , Cleveland, Ohio 44106, United States.
Anthony Malamas
Tesia Shin
Erlei Jin
Yunlu Sun
Zheng-Rong Lu

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Biodegradable Macromolecular Blood Pool Contrast AgentsR01EB000489 · NIBIB · UNIVERSITY OF UTAH · PI LU, ZHENG-RONG · 2003 to 2014
$3.3M
Image-guided EMT inhibition for treating metastatic breast cancerR01CA194518 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI LU, ZHENG-RONG, SCHIEMANN, WILLIAM · 2015 to 2019
$2.4M
NCATS NIH HHS UL1 TR000439NCI NIH HHS R01 CA194518NIBIB NIH HHS EB00489NIBIB NIH HHS R01 EB000489
6 · The paper itself

Abstract

Small interfering RNA (siRNA) has garnered much attention in recent years as a promising avenue for cancer gene therapy due to its ability to silence disease-related genes. Effective gene silencing is contingent upon the delivery of siRNA into the cytosol of target cells and requires the implementation of delivery systems possessing multiple functionalities to overcome delivery barriers. The present work explores the multifunctional properties and biological activity of a recently developed cationic lipid carrier, (1-aminoethyl)iminobis[N-(oleicylcysteinyl-1-amino-ethyl)propionamide]) (ECO). The physicochemical properties and biological activity of ECO/siRNA nanoparticles were assessed over a range of N/P ratios to optimize the formulation. Potent and sustained luciferase silencing in a U87 glioblastoma cell line was observed, even in the presence of serum proteins. ECO/siRNA nanoparticles exhibited pH-dependent membrane disruption at pH levels corresponding to various stages of the intracellular trafficking pathway. It was found that disulfide linkages created during nanoparticle formation enhanced the protection of siRNA from degradation and facilitated site-specific siRNA release in the cytosol by glutathione-mediated reduction. Confocal microscopy confirmed that ECO/siRNA nanoparticles readily escaped from late endosomes prior to cytosolic release of the siRNA cargo. These results demonstrate that the rationally designed multifunctionality of ECO/siRNA nanoparticles is critical for intracellular siRNA delivery and the continuing development of safe and effective delivery systems.

Indexed as

AnimalsBlood ProteinsCationsCell Line, TumorDisulfidesDrug Delivery SystemsEndosomesErythrocytesGene SilencingGlutathioneHemolysisHumansHydrogen-Ion ConcentrationLipidsMicroscopy, ConfocalMicroscopy, FluorescenceBlood ProteinsCationsDisulfidesGlutathioneLipidsRNA, Small Interfering

Identifiers

PMID25020033
PMCPMC4457381

What OpenQuestion holds

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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.