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Updated: Jun 20, 2026

Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis

Preparing a ⁶⁸Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis

Published on: January 7, 2019

Secondary Site Ligand for Integrin αVβ3 Enables Targeted mRNA Delivery.

Sebastian Bayer^1,2, María García-García¹, Raffaele Senatore¹

¹Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.

Angewandte Chemie (International Ed. in English)

|June 18, 2026

Summary

Researchers developed novel small-molecule ligands targeting integrin αVβ3 for enhanced drug delivery. These ligands, displayed multivalently on nanoparticles, enable superselective targeting of tumor endothelial cells, improving mRNA delivery and protein expression.

Keywords:

angiogenesis fragment‐based drug discovery (FBDD)integrin αVβ3 ligand‐directed delivery lipid nanoparticles (LNPs)mRNA delivery multivalency and avidity non‐RGD integrin ligands superselectivity vascular targeting

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Last Updated: Jun 20, 2026

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Published on: April 27, 2017

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Published on: August 12, 2014

Area of Science:

Nanotechnology
Biomedical Engineering
Molecular Biology

Background:

Solid tumor drug delivery is limited by poor perfusion and abnormal vasculature.
Targeting tumor endothelial cells via integrin αVβ3 is a promising strategy.
Existing arginine-glycine-aspartate (RGD) ligands for αVβ3 have high affinity but cause cross-reactivity.

Purpose of the Study:

To develop a novel, selective targeting strategy for αVβ3 using low-affinity ligands displayed multivalently on nanoparticles.
To identify non-orthosteric small-molecule ligands for αVβ3.
To evaluate the efficacy of these ligands for targeted drug delivery via lipid nanoparticles (LNPs).

Main Methods:

Fragment screening was performed under RGD saturation to identify non-orthosteric ligands.
Structure-activity relationship (SAR) analysis determined the binding motif and linker attachment site.
Multivalent display of lead compounds on liposomes and LNPs was achieved for cellular uptake studies.

Main Results:

A 4-methylpyrimidine-2-amine core was identified as a key binding motif.
Fragment-targeted nanoparticles demonstrated superselective uptake in αVβ3-expressing cells.
mRNA delivered by targeted LNPs showed a six-fold increase in functional protein expression compared to controls.

Conclusions:

This study presents the first non-orthosteric, exogenous small-molecule ligands for αVβ3.
Multivalent display of these ligands on nanoparticles enables superselective targeting of αVβ3-overexpressing cells.
This approach offers a promising platform for enhanced, targeted drug delivery to solid tumors.