title: Synthesis of protein-loaded hydrogel particles in an aqueous two-phase system for coincident antigen and CpG oligonucleotide delivery to antigen-presenting cells.
abstract: Materials that effectively deliver protein antigens together with activating ligands to antigen-presenting cells are sought for improved nonviral vaccines. To this end, we synthesized protein-loaded poly(ethylene glycol) (PEG)-based hydrogel particles by cross-linking PEG within the polymer-rich phase of an emulsion formed by a poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) triblock copolymer in saturated aqueous salt solution. These particles (500-nm diameter) contained high levels of encapsulated protein (approximately 75% of dry mass), which was selectively released by proteolytic enzymes normally present in the phagosomal/endosomal compartments of dendritic cells (DCs). For co-delivery of cellular activation signals, gel particles were surface-modified by sequential adsorption of poly(l-arginine) and CpG oligonucleotides. DCs pulsed with protein-loaded particles activated naïve T cells in vitro approximately 10-fold more efficiently than DCs incubated with soluble protein. This organic solvent-free strategy for protein encapsulation within submicron-sized hydrophilic particles is attractive for macromolecule delivery to a variety of phagocytic and nonphagocytic cells.
authors.affiliation: Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Jain
authors.forename: Woon Teck
authors.initials: WT
authors.lastname: Yap
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D000327:Adsorption; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology*; D000941:Antigens / Q000737:chemistry; D018899:CpG Islands; D003713:Dendritic Cells / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D000939:Epitopes / Q000737:chemistry; D018014:Gene Transfer Techniques; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D008956:Models, Chemical; D049329:Nanostructures; D009838:Oligodeoxyribonucleotides / Q000235:genetics*; D009841:Oligonucleotides / Q000737:chemistry; D010047:Ovalbumin / Q000737:chemistry / Q000378:metabolism; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012492:Salts / Q000494:pharmacology; D055672:Static Electricity; D013601:T-Lymphocytes / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
chemical_list: D000941:Antigens; C408982:CPG-oligonucleotide; D004337:Drug Carriers; D000939:Epitopes; D020100:Hydrogels; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D011108:Polymers; D012492:Salts; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D010047:Ovalbumin