Evidence map›Paper›PMID 31853178›Full record

ArticleInternational journal of nanomedicine2019

Thiol-Reactive Star Polymers Functionalized with Short Ethoxy-Containing Moieties Exhibit Enhanced Uptake in Acute Lymphoblastic Leukemia Cells.

Narges Bayat, Nathan McOrist, Nicholas Ariotti, May Lai, Keith Cs Sia, Yuhuan Li, James L Grace, John F Quinn, Michael R Whittaker, Maria Kavallaris and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of nanomedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

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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

12 authors at 4 institutions in 2 countries.

Narges BayatLeukemia Biology Program, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.ORCID 0000-0002-1986-2845
Nathan McOristLeukemia Biology Program, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Nicholas AriottiElectron Microscope Unit, Mark Wainwright Analytical Centre, Chemical Sciences Building, University of New South Wales, Sydney, NSW, Australia.
May LaiARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Keith Cs SiaLeukemia Biology Program, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Yuhuan LiARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.ORCID 0000-0002-1191-0793
James L GraceARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
John F QuinnARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Michael R WhittakerARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Maria KavallarisSchool of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.ORCID 0000-0003-2309-898X
Thomas P Davis *ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.ORCID 0000-0003-2581-4986
Richard B Lock *Leukemia Biology Program, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Cancer Institute of New South Wales · AUMonash University · AUThe University of Queensland · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeDirecting nanoparticles to cancer cells without using antibodies is of great interest. Subtle changes to the surface chemistry of nanoparticles can significantly affect their biological fate, including their propensity to associate with different cell populations. For instance, nanoparticles functionalized with thiol-reactive groups can potentially enhance association with cells that over-express cell-surface thiol groups. The potential of such an approach for enhancing drug delivery for childhood acute lymphoblastic leukemia (ALL) cells has not been investigated. Herein, we investigate the impact of thiol-reactive star polymers on the cellular association and the mechanisms of uptake of the nanoparticles.

methodsWe prepared fluorescently labeled star polymers functionalized with an mPEG brush corona and pyridyl disulfide to examine how reactivity to exofacial thiols impacts cellular association with ALL cells. We also studied how variations to the mPEG brush composition could potentially be used as a secondary method for controlling the extent of cell association. Specifically, we examined how the inclusion of shorter diethylene glycol brush moieties into the nanoparticle corona could be used to further influence cell association.

resultsStar polymers incorporating both thiol-reactive and diethylene glycol brush moieties exhibited the highest cellular association, followed by those functionalized solely with thiol reactive groups compared to control nanoparticles in T and B pediatric ALL patient-derived xenografts harvested from the spleens and bone marrow of immunodeficient mice. Transfection of cells with an early endosomal marker and imaging with correlative light and electron microscopy confirmed cellular uptake. Endocytosis inhibitors revealed dynamin-dependent clathrin-mediated endocytosis as the main uptake pathway for all the star polymers.

conclusionThiol-reactive star polymers having an mPEG brush corona that includes a proportion of diethylene glycol brush moieties represent a potential strategy for improved leukemia cell delivery.

Indexed as

AnimalsCell Line, TumorDrug Delivery SystemsEndocytosisEthylene GlycolsHumansMiceNanoparticlesPolyethylene GlycolsPolymersPrecursor Cell Lymphoblastic Leukemia-LymphomaSulfhydryl CompoundsXenograft Model Antitumor Assaysdiethylene glycolEthylene Glycolsmonomethoxypolyethylene glycolPolyethylene GlycolsPolymersSulfhydryl Compoundsendocytosisflow cytometryleukemiamicroscopynanoparticlestargeting

Identifiers

PMID31853178
PMCPMC6914812
OpenAlexW2996671514

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.