title: Crystalline Oligo(ethylene sulfide) Domains Define Highly Stable Supramolecular Block Copolymer Assemblies.
abstract: With proper control over copolymer design and solvation conditions, self-assembled materials display impressive morphological variety that encompasses nanoscale colloids as well as bulk three-dimensional architectures. Here we take advantage of both hydrophobicity and crystallinity to mediate supramolecular self-assembly of spherical micellar, linear fibrillar, or hydrogel structures by a family of highly asymmetric poly(ethylene glycol)-b-oligo(ethylene sulfide) (PEG-OES) copolymers. Assembly structural polymorphism was achieved with modification of PEG-OES topology (linear versus multiarm) and with precise, monomer-by-monomer control of OES length. Notably, all three morphologies were accessed utilizing OES oligomers with degrees of polymerization as short as three. These exceptionally small assembly forming blocks represent the first application of ethylene sulfide oligomers in supramolecular materials. While the assemblies demonstrated robust aqueous stability over time, oxidation by hydrogen peroxide progressively converted ethylene sulfide residues to increasingly hydrophilic and amorphous sulfoxides and sulfones, causing morphological changes and permanent disassembly. We utilized complementary microscopic and spectroscopic techniques to confirm this chemical stimulus-responsive behavior in self-assembled PEG-OES colloidal dispersions and physical gels. In addition to inherent stimulus-responsive behavior, fibrillar assemblies demonstrated biologically relevant molecular delivery, as confirmed by the dose-dependent activation of murine bone marrow-derived dendritic cells following fibril-mediated delivery of the immunological adjuvant monophosphoryl lipid A. In physical gels composed of either linear or multiarm PEG-OES precursors, rheologic analysis also identified mechanical stimulus-responsive shear thinning behavior. Thanks to the facile preparation, user-defined morphology, aqueous stability, carrier functionality, and stimuli-responsive behaviors of PEG-OES supramolecular assemblies, our findings support a future role for these materials as injectable or implantable biomaterials.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Brubaker
authors.forename: Diana
authors.initials: D
authors.lastname: Velluto
authors.forename: Davide
authors.initials: D
authors.lastname: Demurtas
authors.forename: Edward A
authors.initials: EA
authors.lastname: Phelps
authors.affiliation: ∥Institute for Molecular Engineering, University of Chicago, Chicago, Illinois 60637, United States.|⊥Materials Science Division, Argonne National Laboratory, Argonne, Illinois 60439, United States.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D058105:Polymerization; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D008050:Lipid A; D008823:Micelles; D013440:Sulfides; C000608550:poly(ethylene glycol)-b-oligo(ethylene sulfide); D011092:Polyethylene Glycols; C048436:monophosphoryl lipid A
keywords: cylindrical micelle; hydrogel; micelle; nanoparticle; polymer; self-assembly