Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

Sabrina Valetti, Federica Maione, Simona Mura, Barbara Stella, Didier Desmaële, Magali Noiray, Juliette Vergnaud, Christine Vauthier, Luigi Cattel, Enrico Giraudo, Patrick Couvreur

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)29-39
Number of pages11
JournalJournal of Controlled Release
Volume192
DOIs
Publication statusPublished - Oct 28 2014

Keywords

  • Gemcitabine
  • Pancreatic cancer
  • Squalene nanoparticles
  • Targeted nanoparticles
  • Tumor-targeting peptide

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

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