TY - JOUR
T1 - Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor
AU - Valetti, Sabrina
AU - Maione, Federica
AU - Mura, Simona
AU - Stella, Barbara
AU - Desmaële, Didier
AU - Noiray, Magali
AU - Vergnaud, Juliette
AU - Vauthier, Christine
AU - Cattel, Luigi
AU - Giraudo, Enrico
AU - Couvreur, Patrick
PY - 2014/10/28
Y1 - 2014/10/28
N2 - Chemotherapy for pancreatic cancer is hampered by the tumor's physio-pathological complexity. Here we show a targeted nanomedicine using a new ligand, the CKAAKN peptide, which had been identified by phage display, as an efficient homing device within the pancreatic pathological microenvironment. Taking advantage of the squalenoylation platform, the CKAAKN peptide was conjugated to squalene (SQCKAAKN) and then co-nanoprecipitated with the squalenoyl prodrug of gemcitabine (SQdFdC) giving near monodisperse nanoparticles (NPs) for safe intravenous injection. By interacting with a novel target pathway, the Wnt-2, the CKAAKN functionalization enabled nanoparticles: (i) to specifically interact with both tumor cells and angiogenic vessels and (ii) to simultaneously promote pericyte coverage, thus leading to the normalization of the vasculature likely improving the tumor accessibility for therapy. All together, this approach represents a unique targeted nanoparticle design with remarkable selectivity towards pancreatic cancer and multiple mechanisms of action.
AB - Chemotherapy for pancreatic cancer is hampered by the tumor's physio-pathological complexity. Here we show a targeted nanomedicine using a new ligand, the CKAAKN peptide, which had been identified by phage display, as an efficient homing device within the pancreatic pathological microenvironment. Taking advantage of the squalenoylation platform, the CKAAKN peptide was conjugated to squalene (SQCKAAKN) and then co-nanoprecipitated with the squalenoyl prodrug of gemcitabine (SQdFdC) giving near monodisperse nanoparticles (NPs) for safe intravenous injection. By interacting with a novel target pathway, the Wnt-2, the CKAAKN functionalization enabled nanoparticles: (i) to specifically interact with both tumor cells and angiogenic vessels and (ii) to simultaneously promote pericyte coverage, thus leading to the normalization of the vasculature likely improving the tumor accessibility for therapy. All together, this approach represents a unique targeted nanoparticle design with remarkable selectivity towards pancreatic cancer and multiple mechanisms of action.
KW - Gemcitabine
KW - Pancreatic cancer
KW - Squalene nanoparticles
KW - Targeted nanoparticles
KW - Tumor-targeting peptide
UR - http://www.scopus.com/inward/record.url?scp=84904554609&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904554609&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2014.06.039
DO - 10.1016/j.jconrel.2014.06.039
M3 - Article
C2 - 24984010
AN - SCOPUS:84904554609
VL - 192
SP - 29
EP - 39
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -