TY - JOUR
T1 - Targeting somatostatin receptors by functionalized mesoporous silica nanoparticles-are we striking home?
AU - Paramonov, Valeriy M.
AU - Desai, Diti
AU - Kettiger, Helene
AU - Mamaeva, Veronika
AU - Rosenholm, Jessica M.
AU - Sahlgren, Cecilia
AU - Rivero-Müller, Adolfo
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
KW - CAMP
KW - Ligand-receptor interaction
KW - Mesoporous silica
KW - Somatostatin receptor
KW - Targetability
KW - Targeted nanoparticles/nanopharmaceuticals
UR - http://www.scopus.com/inward/record.url?scp=85074471138&partnerID=8YFLogxK
U2 - 10.7150/ntno.23826
DO - 10.7150/ntno.23826
M3 - Article
C2 - 30148051
AN - SCOPUS:85074471138
VL - 2
SP - 320
EP - 346
JO - Nanotheranostics
JF - Nanotheranostics
SN - 2206-7418
IS - 4
ER -