Evidence map›Paper›PMID 18992290›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2009

Genetically engineering transferrin to improve its in vitro ability to deliver cytotoxins.

Dennis J Yoon, David S H Chu, Christopher W Ng, Edward A Pham, Anne B Mason, David M Hudson, Valerie C Smith, Ross T A MacGillivray, Daniel T Kamei

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 52 citations in OpenAlex.

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  17. The intracellular trafficking pathway of transferrin.Biochimica et biophysica acta · 2012
    Review
  18. Article
  19. Toxin-based targeted therapy for malignant brain tumors.Clinical & developmental immunology · 2012
    Review
  20. Review
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

9 authors at 3 institutions in 2 countries.

Dennis J YoonDepartment of Bioengineering, University of California, Los Angeles, 90095, USA.
David S H Chu
Christopher W Ng
Edward A Pham
Anne B Mason
David M Hudson
Valerie C Smith
Ross T A MacGillivray
Daniel T Kamei
University of California, Los Angeles · USUniversity of British Columbia · CAUniversity of Vermont · US

Funding

Iron Delivery via Blood; Structure Role of TransferrinR01DK021739 · NIDDK · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI MASON, ANNE B. · 1987 to 2011
$3.4M
Iron Delivery via Blood; Structural Role of TransferrinR56DK021739 · NIDDK · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI MASON, ANNE B. · 2006 to 2006
$114k
NIDDK NIH HHS R01 DK021739NIDDK NIH HHS R01 DK21739NIDDK NIH HHS R56 DK021739
6 · The paper itself

Abstract

We previously demonstrated that decreasing the iron release rate of transferrin (Tf), by replacing the synergistic anion carbonate with oxalate, increases its in vitro drug carrier efficacy in HeLa cells. In the current work, the utility of this strategy has been further explored by generating two Tf mutants, K206E/R632A Tf and K206E/K534A Tf, exhibiting different degrees of iron release inhibition. The intracellular trafficking behavior of these Tf mutants has been assessed by measuring their association with HeLa cells. Compared to native Tf, the cellular association of K206E/R632A Tf and K206E/K534A Tf increased by 126 and 250%, respectively. Surface plasmon resonance studies clearly indicate that this increase in cellular association is due to a decrease in the iron release rate and not to differences in binding affinity of the mutants to the Tf receptor (TfR). Diphtheria toxin (DT) conjugates of K206E/R632A Tf and K206E/K534A Tf showed significantly increased cytotoxicity against HeLa cells with IC(50) values of 1.00 pM and 0.93 pM, respectively, compared to a value of 1.73 pM for the native Tf conjugate. Besides further validating our strategy of inhibiting iron release, these Tf mutants provide proof-of-principle that site-directed mutagenesis offers an alternative method for improving the drug carrier efficacy of Tf.

Indexed as

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium SaltAmino Acid SubstitutionBinding, CompetitiveCell ProliferationCytotoxinsDiphtheria ToxinDrug CarriersEdetic AcidEndocytosisHeLa CellsHumansIronKineticsMutationProtein EngineeringReceptors, Transferrin1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium SaltCytotoxinsDiphtheria ToxinDrug CarriersEdetic AcidIronReceptors, TransferrinTransferrin

Identifiers

PMID18992290
PMCPMC2681226
OpenAlexW2007099058

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.