Evidence map›Paper›PMID 29334397›Full record

ArticleNanoscale2018

Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells: a plug-and-play approach.

Sander A A Kooijmans, Jerney J J M Gitz-Francois, Raymond M Schiffelers, Pieter Vader

Open access · hybridAbstract read
In one paragraph

Article in Nanoscale, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

84 citing papers in PubMed, 153 citations in OpenAlex.

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  14. Extracellular vesicle-mediated chemoresistance in breast cancer: focus on miRNA cargo.Extracellular vesicles and circulating nucleic acids · 2025
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24 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Sander A A KooijmansDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands. pvader@umcutrecht.nl.
Jerney J J M Gitz-Francois
Raymond M Schiffelers
Pieter Vader
University Medical Center Utrecht · NL

Funding

European Research Council 260627
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are increasingly being recognized as candidate drug delivery systems due to their ability to functionally transfer biological cargo between cells. However, manipulation of targeting properties of EVs through engineering of the producer cells can be challenging and time-consuming. As a novel approach to confer tumor targeting properties to isolated EVs, we generated recombinant fusion proteins of nanobodies against the epidermal growth factor receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin (C1C2). C1C2-nanobody fusion proteins were expressed in HEK293 cells and isolated from culture medium with near-complete purity as determined by SDS-PAGE. Fusion proteins specifically bound PS and showed no affinity for other common EV membrane lipids. Furthermore, C1C2 fused to anti-EGFR nanobodies (EGa1-C1C2) bound EGFR with high affinity and competed with binding of its natural ligand EGF, as opposed to C1C2 fused to non-targeting control nanobodies (R2-C1C2). Both proteins readily self-associated onto membranes of EVs derived from erythrocytes and Neuro2A cells without affecting EV size and integrity. EV-bound R2-C1C2 did not influence EV-cell interactions, whereas EV-bound EGa1-C1C2 dose-dependently enhanced specific binding and uptake of EVs by EGFR-overexpressing tumor cells. In conclusion, we developed a novel strategy to efficiently and universally confer tumor targeting properties to PS-exposing EVs after their isolation, without affecting EV characteristics, circumventing the need to modify EV-secreting cells. This strategy may also be employed to decorate EVs with other moieties, including imaging probes or therapeutic proteins.

Indexed as

Drug Delivery SystemsExtracellular VesiclesAntigens, SurfaceErbB ReceptorsHEK293 CellsHumansMilk ProteinsPhosphatidylserinesRecombinant Fusion ProteinsSingle-Domain AntibodiesAntigens, SurfaceEGFR protein, humanErbB ReceptorsMFGE8 protein, humanMilk ProteinsPhosphatidylserinesRecombinant Fusion ProteinsSingle-Domain Antibodies

Identifiers

PMID29334397
PMCPMC5795695
OpenAlexW2783798137

What OpenQuestion holds

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LicenceCC BY-NC
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.