Evidence map›Paper›PMID 23036046›Full record

ArticleACS nano2012

Targeting the blind spot of polycationic nanocarrier-based siRNA delivery.

Mengyao Zheng, Giovanni M Pavan, Manuel Neeb, Andreas K Schaper, Andrea Danani, Gerhard Klebe, Olivia M Merkel, Thomas Kissel

Abstract read
In one paragraph

Article in ACS nano, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

40 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Engineering poly- and micelleplexes for nucleic acid delivery - A reflection on their endosomal escape.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Review
  7. Article
  8. Can pulmonary RNA delivery improve our pandemic preparedness?Journal of controlled release : official journal of the Controlled Release Society · 2022
    Article
  9. Article
  10. Charge-Conversion Strategies for Nucleic Acid Delivery.Advanced functional materials · 2021
    Article
  11. Characterization of positively charged polyplexes by tunable resistive pulse sensing.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2021
    Article
  12. Article
  13. T-cell targeted pulmonary siRNA delivery for the treatment of asthma.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2020
    Review
  14. Article
  15. Article
  16. Article
  17. Characterization of spray dried powders with nucleic acid-containing PEI nanoparticles.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019
    Article
  18. Article
  19. Article
  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

8 authors at 2 institutions in 2 countries.

Mengyao ZhengDepartment of Pharmaceutics and Biopharmacy, Philipps-Universität Marburg, Germany.
Giovanni M Pavan
Manuel Neeb
Andreas K Schaper
Andrea Danani
Gerhard Klebe
Olivia M Merkel
Thomas Kissel
Philipps University of Marburg · DEUniversity of Applied Sciences and Arts of Southern Switzerland · CH

Funding

Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4M
NCI NIH HHS P30 CA022453
6 · The paper itself

Abstract

Polycationic nanocarriers attract increasing attention to the field of siRNA delivery. We investigated the self-assembly of siRNA vs pDNA with polycations, which are broadly used for nonviral gene and siRNA delivery. Although polyethyleneimine (PEI) was routinely adopted as siRNA carrier based on its efficacy in delivering pDNA, it has not been investigated yet why PEI efficiently delivers pDNA to cells but is controversially discussed in terms of efficacy for siRNA delivery. We are the first to investigate the self-assembly of PEI/siRNA vs PEI/pDNA and the steps of complexation and aggregation through different levels of hierarchy on the atomic and molecular scale with the novel synergistic use of molecular modeling, molecular dynamics simulation, isothermal titration calorimetry, and other characterization techniques. We are also the fist to elucidate atomic interactions, size, shape, stoichiometry, and association dynamics for polyplexes containing siRNA vs pDNA. Our investigation highlights differences in the hierarchical mechanism of formation of related polycation-siRNA and polycation-pDNA complexes. The results of fluorescence quenching assays indicated a biphasic behavior of siRNA binding with polycations where molecular reorganization of the siRNA within the polycations occurred at lower N/P ratios (nitrogen/phosphorus). Our results, for the first time, emphasize a biphasic behavior in siRNA complexation and the importance of low N/P ratios, which allow for excellent siRNA delivery efficiency. Our investigation highlights the formulation of siRNA complexes from a thermodynamic point of view and opens new perspectives to advance the rational design of new siRNA delivery systems.

Indexed as

Gene SilencingMaterials TestingNanocapsulesParticle SizePolyethyleneimineRNA, Small InterferingTransfectionNanocapsulesPolyethyleneimineRNA, Small Interfering

Identifiers

PMID23036046
PMCPMC3882193
OpenAlexW2005271673

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.