Evidence map›Paper›PMID 30105526›Full record

ArticlePharmaceutical research2018

Bioreducible Poly(Amino Ethers) Based mTOR siRNA Delivery for Lung Cancer.

Nishant S Gandhi, Sudhakar Godeshala, Dana-Lynn T Koomoa-Lange, Bhavani Miryala, Kaushal Rege, Mahavir B Chougule

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Nishant S GandhiDepartment of Pharmaceutical Sciences, The Daniel K Inouye College of pharmacy, University of Hawaii at Hilo, Hilo, HI, 96720, USA.
Sudhakar GodeshalaChemical Engineering, Arizona State University, Tempe, AZ, 85287-6106, USA.
Dana-Lynn T Koomoa-LangeDepartment of Pharmaceutical Sciences, The Daniel K Inouye College of pharmacy, University of Hawaii at Hilo, Hilo, HI, 96720, USA.
Bhavani MiryalaChemical Engineering, Arizona State University, Tempe, AZ, 85287-6106, USA.
Kaushal RegeChemical Engineering, Arizona State University, Tempe, AZ, 85287-6106, USA.
Mahavir B ChouguleDepartment of Pharmaceutical Sciences, The Daniel K Inouye College of pharmacy, University of Hawaii at Hilo, Hilo, HI, 96720, USA. chougule@olemiss.edu.
Arizona State University · USUniversity of Mississippi · USUniversity of Hawaii at Hilo · US

Funding

UH Hilo COP A&RP20GM103466 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI Peter R Hoffmann · 2012 to 2026
$60.3M
Engineering DNA Delivery Polymers using Combinatorial and Cheminformatics MethodsR01GM093229 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI REGE, KAUSHAL · 2011 to 2015
$1.5M
NIGMS NIH HHS P20 GM103466NIGMS NIH HHS R01 GM093229NIH HHS 1R01GM093229-01A1
6 · The paper itself

Abstract

purposeLung cancer is one of the leading causes of deaths in the United States, but currently available therapies for lung cancer are associated with reduced efficacy and adverse side effects. Small interfering RNA (siRNA) can knock down the expression of specific genes and result in therapeutic efficacy in lung cancer. Recently, mTOR siRNA has been shown to induce apoptosis in NSCLC cell lines but its use is limited due to poor stability in biological conditions.

methodsIn this study, we modified an aminoglyocisde-derived cationic poly (amino-ether) by introducing a thiol group using Traut's reagent to generate a bio-reducible modified-poly (amino-ether) (mPAE). The mPAE polymer was used to encapsulate mTOR siRNA by nanoprecipitation method, resulting in the formation of stable and bio-reducible nanoparticles (NPs) which possessed an average diameter of 114 nm and a surface charge of approximately +27 mV.

resultsThe mTOR siRNA showed increased release from the mTS-mPAE NPs in the presence of 10 mM glutathione (GSH). The polymeric mTS-mPAE-NPs were also capable of efficient gene knockdown (60 and 64%) in A549 and H460 lung cancer cells, respectively without significant cytotoxicity at 30 μg/ml concentrations. The NPs also showed time-dependent cellular uptake for up to 24 h as determined using flow cytometry. Delivery of the siRNA using these NPs also resulted in significant inhibition of A549 and H460 cell proliferation in vitro, respectively.

conclusionsThe results demonstrate that the mPAE polymer based NPs show strong potential for siRNA delivery to lung cancer cells. It is anticipated that future modification can help improve the efficacy of nucleic acid delivery, leading to higher inhibition of lung cancer growth in vitro and in vivo.

Indexed as

Antineoplastic AgentsBiological TransportCell Line, TumorCell ProliferationDrug CompoundingEthersHumansLung NeoplasmsOxidation-ReductionPolymersRhodaminesRNA, Small InterferingAntineoplastic AgentsEtherslissamine rhodamine BPolymersRhodaminesRNA, Small Interferingbioreducibledrug deliverylung cancermTORnanomedicinenanoparticlespolymersiRNA

Identifiers

PMID30105526
PMCPMC8463011
OpenAlexW2885433168

What OpenQuestion holds

Textmetadata
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Registered trials

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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.