Evidence map›Paper›PMID 25953848›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Dual targeting of therapeutics to endothelial cells: collaborative enhancement of delivery and effect.

Colin F Greineder, Jacob B Brenza, Ronald Carnemolla, Sergei Zaitsev, Elizabeth D Hood, Daniel C Pan, Bi-Sen Ding, Charles T Esmon, Ann Marie Chacko, Vladimir R Muzykantov

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Nanomedicine-Based Therapeutics to Combat Acute Lung Injury.International journal of nanomedicine · 2021
    Review
  5. Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  6. Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood-brain barrier.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  7. Article
  8. Targeting therapeutics to endothelium: are we there yet?Drug delivery and translational research · 2018
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Targeted endothelial nanomedicine for common acute pathological conditions.Journal of controlled release : official journal of the Controlled Release Society · 2015
    Review
  17. Article
  18. Article
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

10 authors at 1 institution in 1 country.

Colin F Greineder*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Jacob B Brenza*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Ronald Carnemolla*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Sergei Zaitsev*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Elizabeth D Hood*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Daniel C Pan*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Bi-Sen Ding*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Charles T Esmon*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Ann Marie Chacko*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA.
Vladimir R Muzykantov*Department of Pharmacology, Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, and Departments of Radiology and Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA; and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City, Oklahoma, USA muzykant@mail.med.upenn.edu.
Oklahoma Medical Research Foundation · US

Funding

HEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1M
Training in Molecular Therapeutics for Pediatric CardiologyT32HL007915 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI Robert J Levy, JOSEPH W ROSSANO · 1999 to 2026
$13.4M
Protein CoreP01HL110860 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI RAUOVA, LUBICA · 2012 to 2016
$11.4M
Targeted delivery of thrombomodulin in lung diseaseR01HL091950 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2009 to 2013
$1.9M
Howard Hughes Medical InstituteNHLBI NIH HHS P01 HL110860NHLBI NIH HHS R01 HL091950NHLBI NIH HHS R01-HL091950NHLBI NIH HHS T32 HL007439NHLBI NIH HHS T32 HL007915
6 · The paper itself

Abstract

Anchoring pharmacologic agents to the vascular lumen has the potential to modulate critical processes at the blood-tissue interface, avoiding many of the off-target effects of systemically circulating agents. We report a novel strategy for endothelial dual targeting of therapeutics, which both enhances drug delivery and enables targeted agents to partner enzymatically to generate enhanced biologic effect. Based on the recent discovery that paired antibodies directed to adjacent epitopes of platelet endothelial cell adhesion molecule (PECAM)-1 stimulate each other's binding, we fused single-chain fragments (scFv) of paired anti-mouse PECAM-1 antibodies to recombinant murine thrombomodulin (TM) and endothelial protein C receptor (EPCR), endothelial membrane proteins that partner in activation of protein C (PC). scFv/TM and scFv/EPCR bound to mouse endothelial PECAM-1 with high affinity (EC50 1.5 and 3.8 nM, respectively), and codelivery induced a 5-fold increase in PC activation not seen when TM and EPCR are anchored to distinct cell adhesion molecules. In a mouse model of acute lung injury, dual targeting reduces both the expression of lung inflammatory markers and trans-endothelial protein leak by as much as 40%, as compared to either agent alone. These findings provide proof of principle for endothelial dual targeting, an approach with numerous potential biomedical applications.

Indexed as

Acute Lung InjuryAnimalsCell Adhesion MoleculesCell Line, TumorDisease Models, AnimalDrug Delivery SystemsEndothelial CellsEndothelium, VascularEpitopesHumansMaleMiceMice, Inbred C57BLPharmaceutical PreparationsPlatelet Endothelial Cell Adhesion Molecule-1Protein CCell Adhesion MoleculesEpitopesPharmaceutical PreparationsPlatelet Endothelial Cell Adhesion Molecule-1Protein CReceptors, Cell SurfaceThrombomodulindrug deliveryEPCRPECAM-1thrombomodulin

Identifiers

PMID25953848
PMCPMC4511192
OpenAlexW2130017009

What OpenQuestion holds

Textmetadata
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.