title: Intracellular targeting of PLGA nanoparticles encapsulating antigenic peptide to the endoplasmic reticulum of dendritic cells and its effect on antigen cross-presentation in vitro.
abstract: Intracellularly targeted delivery system based on PLGA nanoparticles decorated with endoplasmic reticulum (ER)-targeting or control peptides and encapsulating antigenic peptide and fluorescent marker, was developed and characterized. The cellular uptake by dendritic cells (murine DC2.4 cells), intracellular trafficking, and cross-presentation efficiency of this delivery system were studied in vitro. The prepared nanoparticles (an average diameter of ~350 nm) efficiently encapsulated antigenic peptide and fluorescent marker and gradually released them over several days. Yet, the nanoparticles' size was small enough to allow their efficient endocytosis by the antigen-presenting cells in vitro. Surface conjugation of the targeting or control peptides enhanced the endocytosis of the nanoparticles, affected their intracellular trafficking, and induced prolonged low-magnitude cross-presentation of the antigenic peptide. We demonstrated in vitro that the intracellular fate of nanoparticulate drug delivery systems can be altered by their surface decoration with peptidic targeting residues. More detailed investigation is required to determine the mechanisms and therapeutic potential of intracellular targeting of nanodelivery systems in vivo for the goal of an anticancer vaccine.
authors.affiliation: Department of Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Sneh-Edri
authors.forename: Diana
authors.initials: D
authors.lastname: Likhtenshtein
authors.forename: David
authors.initials: D
authors.lastname: Stepensky
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D002460:Cell Line; D045142:Cross-Priming; D020285:Cryoelectron Microscopy; D003713:Dendritic Cells / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D010446:Peptide Fragments; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid