title: Peptide conjugation: before or after nanoparticle formation?
abstract: We report herein a detailed study concerning the impact of different bioconjugation and nanoformulation strategies on the in vitro targeting ability of peptide-decorated squalenoyl gemcitabine (SQdFdC) nanoparticles (NPs). NPs have been functionalized with the CKAAKN peptide, previously identified as an efficient homing device within the pancreatic pathological microenvironment. Two approaches have been followed: (i) either the CKAAKN peptide was directly conjugated at the surface of preformed SQdFdC nanoparticles (conjugation after NP formation) or (ii) it was first reacted with a maleimide squalenoyl derivative before the resulting bioconjugate was co-nanoprecipitated with SQdFdC to form the peptide-decorated NPs (conjugation before NP formation). NPs were characterized with respect to mean diameter, zeta potential, and stability over time. Then, their specific interaction with the sFRP-4 protein was evaluated by surface plasmon resonance. Although both synthetic strategies allowed us to formulate NPs able to interact with the corresponding receptor, enhanced target binding and better specific avidity were observed with CKAAKN-NPs functionalized before NP formation. These NPs displayed the highest cell uptake and cytotoxicity in an in vitro model of human MIA Paca-2 pancreatic cancer cells.
authors.affiliation: Université Paris-Sud , Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry cedex, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Valetti
authors.forename: Simona
authors.initials: S
authors.lastname: Mura
authors.forename: Magali
authors.initials: M
authors.lastname: Noiray
authors.forename: Silvia
authors.initials: S
authors.lastname: Arpicco
authors.forename: Franco
authors.initials: F
authors.lastname: Dosio
authors.forename: Juliette
authors.initials: J
authors.lastname: Vergnaud
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.forename: Barbara
authors.initials: B
authors.lastname: Stella
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008024:Ligands; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000093542:Gemcitabine; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D003841:Deoxycytidine; D004337:Drug Carriers; D008024:Ligands; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D000093542:Gemcitabine; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins