ArticleACS nano2015
Collaborative Enhancement of Endothelial Targeting of Nanocarriers by Modulating Platelet-Endothelial Cell Adhesion Molecule-1/CD31 Epitope Engagement.
Article in ACS nano, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of global and high throughput public gene array data for robust vascular gene expression discovery in chronic rhinosinusitis: Implications in controlled release.Journal of controlled release : official journal of the Controlled Release Society · 2021Pooled it
- Platelet-derived biomimetic nanoplatforms: a promising drug delivery strategy for cardiovascular disease.Journal of nanobiotechnology · 2025Review
- Nanocarriers for targeted drug delivery in the vascular system: focus on endothelium.Journal of nanobiotechnology · 2024Review
- Sex-based differences of antioxidant enzyme nanoparticle effects following traumatic brain injury.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Targeting vascular inflammation through emerging methods and drug carriers.Advanced drug delivery reviews · 2022Review
- Targeting pulmonary vascular endothelial cells for the treatment of respiratory diseases.Frontiers in pharmacology · 2022Review
- 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 · 2020Article
- Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Targeting therapeutics to endothelium: are we there yet?Drug delivery and translational research · 2018Review
- Focus on Fundamentals: Achieving Effective Nanoparticle Targeting.Trends in molecular medicine · 2018Review
- The Multifaceted Uses and Therapeutic Advantages of Nanoparticles for Atherosclerosis Research.Materials (Basel, Switzerland) · 2018Review
- Vascular endothelial effects of collaborative binding to platelet/endothelial cell adhesion molecule-1 (PECAM-1).Scientific reports · 2018Article
- Nanoparticle targeting to the endothelium during normothermic machine perfusion of human kidneys.Science translational medicine · 2017Article
- Article
- Vascular-targeted nanocarriers: design considerations and strategies for successful treatment of atherosclerosis and other vascular diseases.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2016Review
- Molecular engineering of high affinity single-chain antibody fragment for endothelial targeting of proteins and nanocarriers in rodents and humans.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Nanocarriers (NCs) coated with antibodies (Abs) to extracellular epitopes of the transmembrane glycoprotein PECAM (platelet endothelial cell adhesion molecule-1/CD31) enable targeted drug delivery to vascular endothelial cells. Recent studies revealed that paired Abs directed to adjacent, yet distinct epitopes of PECAM stimulate each other's binding to endothelial cells in vitro and in vivo ("collaborative enhancement"). This phenomenon improves targeting of therapeutic fusion proteins, yet its potential role in targeting multivalent NCs has not been addressed. Herein, we studied the effects of Ab-mediated collaborative enhancement on multivalent NC spheres coated with PECAM Abs (Ab/NC, ∼180 nm diameter). We found that PECAM Abs do mutually enhance endothelial cell binding of Ab/NC coated by paired, but not "self" Ab. In vitro, collaborative enhancement of endothelial binding of Ab/NC by paired Abs is modulated by Ab/NC avidity, epitope selection, and flow. Cell fixation, but not blocking of endocytosis, obliterated collaborative enhancement of Ab/NC binding, indicating that the effect is mediated by molecular reorganization of PECAM molecules in the endothelial plasmalemma. The collaborative enhancement of Ab/NC binding was affirmed in vivo. Intravascular injection of paired Abs enhanced targeting of Ab/NC to pulmonary vasculature in mice by an order of magnitude. This stimulatory effect greatly exceeded enhancement of Ab targeting by paired Abs, indicating that '"collaborative enhancement"' effect is even more pronounced for relatively large multivalent carriers versus free Abs, likely due to more profound consequences of positive alteration of epitope accessibility. This phenomenon provides a potential paradigm for optimizing the endothelial-targeted nanocarrier delivery of therapeutic agents.
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Registered trials
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.