Evidence map›Paper›PMID 24320687›Full record

ArticleBioconjugate chemistry2014

Differential polymer structure tunes mechanism of cellular uptake and transfection routes of poly(β-amino ester) polyplexes in human breast cancer cells.

Jayoung Kim, Joel C Sunshine, Jordan J Green

Abstract read
In one paragraph

Article in Bioconjugate chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

49 citing papers in PubMed, 85 citations in OpenAlex.

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  10. Nonviral nanoparticle gene delivery into the CNS for neurological disorders and brain cancer applications.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023
    Review
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  17. High-throughput evaluation of polymeric nanoparticles for tissue-targeted gene expression using barcoded plasmid DNA.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Article
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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

3 authors at 1 institution in 1 country.

Jayoung KimDepartment of Biomedical Engineering and the Translational Tissue Engineering Center and §Department of Ophthalmology, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.
Joel C Sunshine
Jordan J Green
Johns Hopkins University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
Gene Delivery Nanoparticles to Treat GlioblastomaR01EB016721 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2013 to 2017
$1.9M
Nanoparticle-mediated peptide delivery for breast cancerR21CA152473 · NCI · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2011 to 2012
$392k
NCI NIH HHS R21 CA152473NCI NIH HHS R21CA152473NEI NIH HHS EY001765NEI NIH HHS P30 EY001765NIBIB NIH HHS R01 EB016721NIBIB NIH HHS R01EB016721NIGMS NIH HHS T32 GM007309
6 · The paper itself

Abstract

Successful gene delivery with nonviral particles has several barriers, including cellular uptake, endosomal escape, and nuclear transport. Understanding the mechanisms behind these steps is critical to enhancing the effectiveness of gene delivery. Polyplexes formed with poly(β-amino ester)s (PBAEs) have been shown to effectively transfer DNA to various cell types, but the mechanism of their cellular uptake has not been identified. This is the first study to evaluate the uptake mechanism of PBAE polyplexes and the dependence of cellular uptake on the end group and molecular weight of the polymer. We synthesized three different analogues of PBAEs with the same base polymer poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) (B4S4) but with small changes in the end group or molecular weight. We quantified the uptake and transfection efficiencies of the pDNA polyplexes formulated from these polymers in hard-to-transfect triple negative human breast cancer cells (MDA-MB 231). All polymers formed positively charged (10-17 mV) nanoparticles of ∼200 nm in size. Cellular internalization of all three formulations was inhibited the most (60-90% decrease in cellular uptake) by blocking caveolae-mediated endocytosis. Greater inhibition was shown with polymers that had a 1-(3-aminopropyl)-4-methylpiperazine end group (E7) than the others with a 2-(3-aminopropylamino)-ethanol end group (E6) or higher molecular weight. However, caveolae-mediated endocytosis was generally not as efficient as clathrin-mediated endocytosis in leading to transfection. These findings indicate that PBAE polyplexes can be used to transfect triple negative human breast cancer cells and that small changes to the same base polymer can modulate their cellular uptake and transfection routes.

Indexed as

CaveolaeEndocytosisHumansMolecular StructureMolecular WeightNanoparticlesParticle SizePolymersSurface PropertiesTransfectionTumor Cells, Culturedpoly(beta-amino ester)Polymers

Identifiers

PMID24320687
PMCPMC4016154
OpenAlexW2333965372

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.