Abstract
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.
Original language | English |
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Pages (from-to) | 320-346 |
Number of pages | 27 |
Journal | Nanotheranostics |
Volume | 2 |
Issue number | 4 |
DOIs | |
Publication status | Published - Jan 2018 |
Funding
Our work was supported by European Community Mobility Programme EMA2 (grant #372117-1-2012-1-FI-ERAMUNDUS-EMA21; to VMP), Turku Doctoral Programme of Molecular Medicine (TuDMM; to VMP), K. Albin Johanssons stiftelse (to VMP), Ida Montinin Säätiö (to VMP), Pentti and Tyyni Ekbom foundation (to VMP), Instrumentariumin tiedesäätiö (to VMP), Cancer Society of Finland (to DD), Finnish Cultural Foundation (to DD), The Swiss National Science Foundation (project #P2BSP3_161928; to HK), Sigrid Juselius Foundation (to VM), Jane and Aatos Erkko foundation (to DD, JR), Academy of Finland (project #284542, 309374; to CS, JR), Turku University Foundation (to ARM).
Keywords
- CAMP
- Ligand-receptor interaction
- Mesoporous silica
- Somatostatin receptor
- Targetability
- Targeted nanoparticles/nanopharmaceuticals