Evidence map›Paper›PMID 25301142›Full record

ArticleMolecular pharmaceutics2014

Distinct subcellular trafficking resulting from monomeric vs multimeric targeting to endothelial ICAM-1: implications for drug delivery.

Rasa Ghaffarian, Silvia Muro

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  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. Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme.Journal of controlled release : official journal of the Controlled Release Society · 2020
    Article
  7. Review
  8. The Journal of pharmacology and experimental therapeutics · 2019
    Article
  9. Article
  10. Review
  11. Article
  12. Intra- and trans-cellular delivery of enzymes by direct conjugation with non-multivalent anti-ICAM molecules.Journal of controlled release : official journal of the Controlled Release Society · 2016
    Article
  13. Article
  14. 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

2 authors.

Rasa GhaffarianFischell Department of Bioengineering, University of Maryland , 2330 Jeong H. Kim Engineering Building, College Park, Maryland 20742, United States.
Silvia Muro

Funding

Targeted replacement of defective lysosomal enzymes in the lung and brainR01HL098416 · NHLBI · UNIV OF MARYLAND, COLLEGE PARK · PI MURO, SILVIA · 2010 to 2020
$3.3M
NHLBI NIH HHS R01 HL098416NHLBI NIH HHS R01-HL98416
6 · The paper itself

Abstract

Ligand-targeted, receptor-mediated endocytosis is commonly exploited for intracellular drug delivery. However, cells-surface receptors may follow distinct endocytic fates when bound by monomeric vs multimeric ligands. Our purpose was to study this paradigm using ICAM-1, an endothelial receptor involved in inflammation, to better understand its regulation and potential for drug delivery. Our procedure involved fluorescence microscopy of human endothelial cells to determine the endocytic behavior of unbound ICAM-1 vs ICAM-1 bound by model ligands: monomeric (anti-ICAM) vs multimeric (anti-ICAM biotin-streptavidin conjugates or anti-ICAM coated onto 100 nm nanocarriers). Our findings suggest that both monomeric and multimeric ligands undergo a similar endocytic pathway sensitive to amiloride (∼50% inhibition), but not inhibitors of clathrin-pits or caveoli. After 30 min, ∼60-70% of both ligands colocalized with Rab11a-compartments. By 3-5 h, ∼65-80% of multimeric anti-ICAM colocalized with perinuclear lysosomes with ∼60-80% degradation, while 70% of monomeric anti-ICAM remained associated with Rab11a at the cell periphery and recycled to and from the cell-surface with minimal (<10%) lysosomal colocalization and minimal (≤15%) degradation. In the absence of ligands, ICAM-1 also underwent amiloride-sensitive endocytosis with peripheral distribution, suggesting that monomeric (not multimeric) anti-ICAM follows the route of this receptor. In conclusion, ICAM-1 can mediate different intracellular itineraries, revealing new insight into this biological pathway and alternative avenues for drug delivery.

Indexed as

Cell LineDrug CarriersDrug Delivery SystemsEndothelial CellsHumansIntercellular Adhesion Molecule-1Drug CarriersIntercellular Adhesion Molecule-1CAM-mediated endocytosisintracellular traffickingreceptor-mediated endocytosistargeted drug carriersvascular endothelium

Identifiers

PMID25301142
PMCPMC4255724

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.