Evidence map›Paper›PMID 23239010›Full record

ArticlePharmaceutical research2013

Cellular uptake mechanisms of novel anionic siRNA lipoplexes.

Mamta Kapoor, Diane J Burgess

Abstract read
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Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Anti-F1000Research · 2020
    Article
  5. The pervasiveness of macropinocytosis in oncological malignancies.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019
    Review
  6. Article
  7. Article
  8. Non-viral nanocarriers for siRNA delivery in breast cancer.Journal of controlled release : official journal of the Controlled Release Society · 2014
    Review
  9. Article
  10. 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

2 authors.

Mamta KapoorDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, Connecticut 06269, USA.
Diane J Burgess

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo investigate cellular uptake pathways of novel anionic siRNA-lipoplexes as a function of formulation composition.

methodsAnionic formulations with anionic lipid/Ca(2+)/siRNA ratio of 1.3/2.5/1 (AF1) and 1.3/0.3/1 (AF2) were utilized. Uptake mechanisms were investigated using uptake inhibition and co-localization approaches in breast cancer cells. Actin-mediated uptake was investigated using actin polymerization and rearrangement assays. Silencing efficiency and endosomal escaping capability of lipoplexes were evaluated. The cationic formulation Lipofectamine-2000 was used as a control.

resultsAnionic lipoplexes entered the breast cancer cells via endocytosis specifically via macropinocytosis or via both macropinocytosis and HSPG (heparin sulfate proteoglycans) pathways, depending on the Ca(2+)/siRNA ratio. Additionally, uptake of these lipoplexes was both microtubule and actin dependent. The control cationic lipid-siRNA complexes (Lipofectamine-2000) were internalized via both endocytic (phagocytosis, HSPG) and non-endocytic (membrane fusion) pathways. Their uptake was microtubule independent but actin dependent. Silencing efficiency of the AF2 formulation was negligible mainly due to poor endosomal release (rate-limiting step).

conclusionsFormulation composition significantly influences the internalization mechanism of anionic lipoplexes. Uptake mechanism together with formulation bioactivity helped in identification of the rate-limiting steps to efficient siRNA delivery. Such studies are extremely useful for formulation optimization to achieve enhanced intracellular delivery of nucleic acids.

Indexed as

ActinsAnionsBreastBreast NeoplasmsCalciumCell Line, TumorFemaleHumansLipidsPinocytosisRNA InterferenceRNA, Small InterferingActinsAnionsCalciumLipidsLipofectamineRNA, Small Interfering

Identifiers

PMID23239010

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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.