Evidence map›Paper›PMID 27210108›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2016

Size and targeting to PECAM vs ICAM control endothelial delivery, internalization and protective effect of multimolecular SOD conjugates.

Vladimir V Shuvaev, Silvia Muro, Evguenia Arguiri, Makan Khoshnejad, Samira Tliba, Melpo Christofidou-Solomidou, Vladimir R Muzykantov

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Review
  3. Optimizing mRNA delivery with targeted elastin-like polypeptide-based LENN formulations: Insights into the endocytosis mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  4. Equip your vehicle for the right terrain: Using features of local pathology to guide engineering of targeted drug delivery systems.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
  5. Article
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  7. Sex-based differences of antioxidant enzyme nanoparticle effects following traumatic brain injury.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Article
  8. Review
  9. Review
  10. Overcoming Vascular Barriers to Improve the Theranostic Outcomes of Nanomedicines.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. 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
  18. Article
  19. Review
  20. 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

7 authors at 3 institutions in 1 country.

Vladimir V ShuvaevDepartment of Systems Pharmacology and Translational Therapeutics, Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Silvia MuroFischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Evguenia ArguiriDepartment of Medicine, Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Makan KhoshnejadDepartment of Systems Pharmacology and Translational Therapeutics, Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Samira TlibaDepartment of Systems Pharmacology and Translational Therapeutics, Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Melpo Christofidou-SolomidouDepartment of Medicine, Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Vladimir R MuzykantovDepartment of Systems Pharmacology and Translational Therapeutics, Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: muzykant@mail.med.upenn.edu.
University of Pennsylvania · USTranslational Therapeutics (United States) · USUniversity of Maryland, College Park · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3M
Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
Targeted nanomedicine for ALI and I/RR01HL125462 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.3M
Targeting Carriers with Controlled Geometry to EndotheliumR01HL087036 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2008 to 2012
$2.0M
Endothelial targeting of antioxidantsR01HL126874 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2016 to 2019
$1.7M
Augmentation of Antioxidant Defenses by ImmunotargetingR01HL073940 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2004 to 2007
$1.6M
NHLBI NIH HHS R01 HL073940NHLBI NIH HHS R01 HL087036NHLBI NIH HHS R01 HL125462NHLBI NIH HHS R01 HL126874NHLBI NIH HHS T32 HL007954NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

Controlled endothelial delivery of SOD may alleviate abnormal local surplus of superoxide involved in ischemia-reperfusion, inflammation and other disease conditions. Targeting SOD to endothelial surface vs. intracellular compartments is desirable to prevent pathological effects of external vs. endogenous superoxide, respectively. Thus, SOD conjugated with antibodies to cell adhesion molecule PECAM (Ab/SOD) inhibits pro-inflammatory signaling mediated by endogenous superoxide produced in the endothelial endosomes in response to cytokines. Here we defined control of surface vs. endosomal delivery and effect of Ab/SOD, focusing on conjugate size and targeting to PECAM vs. ICAM. Ab/SOD enlargement from about 100 to 300nm enhanced amount of cell-bound SOD and protection against extracellular superoxide. In contrast, enlargement inhibited endocytosis of Ab/SOD and diminished mitigation of inflammatory signaling of endothelial superoxide. In addition to size, shape is important: endocytosis of antibody-coated spheres was more effective than that of polymorphous antibody conjugates. Further, targeting to ICAM provides higher endocytic efficacy than targeting to PECAM. ICAM-targeted Ab/SOD more effectively mitigated inflammatory signaling by intracellular superoxide in vitro and in animal models, although total uptake was inferior to that of PECAM-targeted Ab/SOD. Therefore, both geometry and targeting features of Ab/SOD conjugates control delivery to cell surface vs. endosomes for optimal protection against extracellular vs. endosomal oxidative stress, respectively.

Indexed as

AnimalsAntibodies, MonoclonalDrug Delivery SystemsEndocytosisEndosomesEndothelium, VascularEndotoxemiaHuman Umbilical Vein Endothelial CellsImmunoconjugatesIntercellular Adhesion Molecule-1Mice, Inbred C57BLNanoparticlesOxidative StressPlatelet Endothelial Cell Adhesion Molecule-1Superoxide DismutaseSuperoxidesAntibodies, MonoclonalImmunoconjugatesIntercellular Adhesion Molecule-1Platelet Endothelial Cell Adhesion Molecule-1Superoxide DismutaseSuperoxidesCell adhesion moleculesEndocytosisEndothelial cellsIntracellular deliveryVascular immunotargeting

Identifiers

PMID27210108
PMCPMC4916012
OpenAlexW2395032546

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.