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The concept of delivering nanoformulations to desired tissues by means of targeting membrane receptors of high local abundance by ligands anchored to the nanocarrier has gained a lot of attention over the last decade. Currently, there is no unanimous opinion on whether surface functionalization of nanocarriers by targeting ligands translates into any real benefit in terms of pharmacokinetics or treatment outcomes. Having examined the published nanocarriers designed to engage with somatostatin receptors, we realized that in the majority of cases targetability claims were not supported by solid evidence of targeting ligand-targeted receptor coupling, which is the very crux of a targetability concept. Here, we present an approach to characterize targetability of mesoporous silica-based nanocarriers functionalized with ligands of somatostatin receptors. The targetability proof in our case comes from a functional assay based on a genetically-encoded cAMP probe, which allows for real-time capture of receptor activation in living cells, triggered by targeting ligands on nanoparticles. We elaborate on the development and validation of the assay, highlighting the power of proper functional tests in the characterization pipeline of targeted nanoformulations.
- mesoporous silica nanoparticles
- cancer therapy
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