Evidence map›Paper›PMID 22532601›Full record

ArticleMolecular cancer therapeutics2012

Thermal targeting of an acid-sensitive doxorubicin conjugate of elastin-like polypeptide enhances the therapeutic efficacy compared with the parent compound in vivo.

Shama Moktan, Eddie Perkins, Felix Kratz, Drazen Raucher

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

Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
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  20. Applications of elastin-like polypeptides in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2014
    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

4 authors at 1 institution in 1 country.

Shama MoktanDepartment of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Eddie Perkins
Felix Kratz
Drazen Raucher
University of Mississippi Medical Center · US

Funding

Thermally Targeted Cell Cycle Inhibitors for the Treatment of Pancreatic CancerR21CA137418 · NCI · UNIVERSITY OF MISSISSIPPI MED CTR · PI RAUCHER, DRAZEN · 2010 to 2011
$352k
Thermally Targeted Delivery of c-Myc Inhibitory Polypeptides to Malignant GliomasR21CA139589 · NCI · UNIVERSITY OF MISSISSIPPI MED CTR · PI RAUCHER, DRAZEN · 2010 to 2011
$341k
Targeted Delivery of c-Myc Inhibitory PolypeptidesR21CA113813 · NCI · UNIVERSITY OF MISSISSIPPI MED CTR · PI RAUCHER, DRAZEN · 2006 to 2007
$277k
Thermally Targeted Delivery of Therapeutic PeptidesR43CA135799 · NCI · THERMALLY TARGETED THERAPEUTICS · PI RAUCHER, DRAZEN · 2009 to 2009
$139k
NCI NIH HHS 1R21CA137418-01A2NCI NIH HHS 1R21CA139589-01NCI NIH HHS R21 CA113813NCI NIH HHS R21 CA137418NCI NIH HHS R21 CA139589NCI NIH HHS R43 CA135799
6 · The paper itself

Abstract

Elastin-like polypeptides (ELP) aggregate in response to mild hyperthermia, but remain soluble under normal physiologic conditions. ELP macromolecules can accumulate in solid tumors because of the enhanced permeability and retention effect. Tumor retention of ELPs can be further enhanced through hyperthermia-induced aggregation of ELPs by local heating of the tumor. We evaluated the therapeutic potential of ELPs in delivering doxorubicin in the E0771 syngeneic mouse breast cancer model. The ELP-Dox conjugate consisted of a cell-penetrating peptide at the N-terminus and the 6-maleimidocaproyl hydrazone derivative of doxorubicin at the C-terminus of ELP. The acid-sensitive hydrazone linker ensured release of doxorubicin in the lysosomes/endosomes after cellular uptake of the drug conjugate. ELP-Dox dosed at 5 mg doxorubicin equivalent/kg, extended the plasma half-life of doxorubicin to 5.5 hours. In addition, tumor uptake of ELP-Dox increased 2-fold when hyperthermia was applied, and was also enhanced compared to free doxorubicin. Although high levels of doxorubicin were found in the heart of animals treated with free doxorubicin, no detectable levels of doxorubicin were found in ELP-Dox-treated animals, indicating a correlation between tumor targeting and reduction of potential cardiac toxicity by ELP-Dox. At an optimal dose of 12 mg doxorubicin equivalent/kg, ELP-Dox in combination with hyperthermia induced a complete tumor growth inhibition, which was distinctly superior to free drug that only moderately inhibited tumor growth. In summary, our findings show that thermal targeting of ELP increases the potency of doxorubicin underlying the potential of exploiting ELPs to enhance the therapeutic efficacy of conventional anticancer drugs.

Indexed as

Hyperthermia, InducedAnimalsBiological TransportCell Line, TumorCell-Penetrating PeptidesCombined Modality TherapyDisease Models, AnimalDoxorubicinElastinFemaleHumansMaximum Tolerated DoseMiceMice, Inbred C57BLNeoplasmsCell-Penetrating PeptidesDoxorubicinElastin

Identifiers

PMID22532601
PMCPMC3392364
OpenAlexW2125284587

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.