title: VPAC receptor mediated tumor cell targeting by protamine based nanoparticles.
abstract: The receptors for vasoactive intestinal peptide (VIP), VPAC1-, VPAC2-, and PAC1-receptor are overexpressed by various tumor cells. VIP can target these receptors and transport conjugates into the cell. However, the use of VIP for tumor cell targeting is hampered by the peptides short half-lives due to enzymatic degradation. Because protamine-based nanoparticles (proticles) protect the peptide and serve as peptide depot, we explored the potential of proticles as carrier for VIP-conjugated molecules. The VIP-loaded proticles were stable as shown by Fluorescence Correlation Spectroscopy. With Confocal Laser Scanning Microscopy, we observed VIP-loaded proticles to specifically target the tumor cells. The cell binding triggered the substance release and conjugate internalization of VIP-Cy3 in vitro and ex vivo by human tumors. We observed VIP releasing proticle depots distributed in rat tissue and human tumors. Our findings warrant further studies to explore the proticles potential to enable peptide-mediated targeting for in vivo and clinical applications.
authors.affiliation: Institute of Cancer Research, Medical University of Vienna, KIM-1, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Ortner
authors.forename: Karin
authors.initials: K
authors.lastname: Wernig
authors.forename: Raphaela
authors.initials: R
authors.lastname: Kaisler
authors.forename: Michael
authors.initials: M
authors.lastname: Edetsberger
authors.forename: Franz
authors.initials: F
authors.lastname: Hajos
authors.forename: Gottfried
authors.initials: G
authors.lastname: Köhler
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Mosgoeller
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004355:Drug Stability; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D011479:Protamines / Q000737:chemistry*; D051381:Rats; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000096:biosynthesis*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000096:biosynthesis*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000096:biosynthesis*; D013050:Spectrometry, Fluorescence; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D011479:Protamines; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide