Evidence map›Paper›PMID 32167754›Full record

ArticleBioconjugate chemistry2020

Molecularly Engineered Nanobodies for Tunable Pharmacokinetics and Drug Delivery.

Patrick M Glassman, Landis R Walsh, Carlos H Villa, Oscar A Marcos-Contreras, Elizabeth D Hood, Vladimir R Muzykantov, Colin F Greineder

Open access · greenAbstract read
In one paragraph

Article in Bioconjugate chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Affinity- and Format-Dependent Pharmacokinetics ofPharmaceuticals (Basel, Switzerland) · 2026
    Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023
    Review
  11. Article
  12. Overcoming Vascular Barriers to Improve the Theranostic Outcomes of Nanomedicines.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Review
  13. Review
  14. Applications of nanobodies in brain diseases.Frontiers in immunology · 2022
    Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. 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

7 authors at 2 institutions in 1 country.

Patrick M GlassmanDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0003-3786-0437
Landis R WalshDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Carlos H VillaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Oscar A Marcos-ContrerasDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Elizabeth D HoodDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0002-6829-8339
Vladimir R MuzykantovDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Colin F GreinederDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0001-9740-7672
Translational Therapeutics (United States) · USUniversity of Michigan · US

Funding

TRAINING GRANT IN HEMOSTASIS AND THROMBOSIST32HL007971 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rodney M Camire · 2001 to 2026
$10.6M
Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
TRANSFUSION MEDICINE RESEARCH TRAINING PROGRAMT32HL007775 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SIEGEL, DONALD LAWRENCE · 1993 to 2023
$2.8M
Endothelial targeting of antioxidantsR01HL126874 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2016 to 2019
$1.7M
ICAM-1 targeted thrombomodulin: an experimental therapeutic for the Acute Respiratory Distress SyndromeK08HL130430 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GREINEDER, COLIN FRED · 2016 to 2020
$665k
NHLBI NIH HHS K08 HL130430NHLBI NIH HHS R01 HL126874NHLBI NIH HHS T32 HL007775NHLBI NIH HHS T32 HL007954NHLBI NIH HHS T32 HL007971
6 · The paper itself

Abstract

The use of single-domain antibody fragments, or nanobodies, has gained popularity in recent years as an alternative to traditional monoclonal antibody-based approaches. Relatively little is known, however, about the utility of nanobodies as targeting agents for delivery of therapeutic cargoes, particularly to vascular epitopes or in the setting of acute inflammatory conditions. We used a nanobody (VCAMelid) directed against mouse vascular cell adhesion molecule 1 (VCAM-1) and techniques for site-specific radiolabeling and bioconjugation to measure targeting to sites of constitutive and inducible antigen expression and investigate the impact of various characteristics (affinity, valence, circulation time) on nanobody biodistribution and pharmacokinetics. Engineering of VCAMelid for bivalent binding (BiVCAMelid) increased affinity by an order of magnitude and provided 2.8- and 3.6-fold enhancements in splenic and brain targeting in naive mice, with a further 2.6-fold increase in brain uptake in the setting of focal CNS inflammation. In contrast, introduction of an albumin-binding arm (VCAM/ALB8) did not affect binding affinity, but its prolonged circulation time resulted in 3.5-fold and 17.4-fold increases in splenic and brain uptake at 20 min post-dose and remarkable 40-, 25-, and 15-fold enhancements in overall exposure of blood, spleen, and brain, respectively, relative to both VCAMelid and BiVCAMelid. Both therapeutic protein (superoxide dismutase, SOD-1) and nanocarrier (liposome) delivery were enhanced by conjugation to VCAM-1 targeted nanobodies. The bispecific VCAM/ALB8 maintained its superiority over VCAMelid in enhancing both circulation time and organ targeting of SOD-1, but its advantages were largely blunted by conjugation to liposomes.

Indexed as

Protein EngineeringAnimalsBiological TransportBrainDrug CarriersIsotope LabelingMiceSingle-Domain AntibodiesSpleenTissue DistributionVascular Cell Adhesion Molecule-1Drug CarriersSingle-Domain AntibodiesVascular Cell Adhesion Molecule-1

Identifiers

PMID32167754
PMCPMC7413641
OpenAlexW3012530015

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.