A microfluidic platform for the synthesis of polymer and polymer-protein-based protocells.

In this study, we demonstrate the fabrication of polymersomes, protein-blended polymersomes, and polymeric microcapsules using droplet microfluidics. Polymersomes with uniform, single bilayers and controlled diameters are assembled from water-in-oil-in-water double-emulsion droplets. This technique relies on adjusting the interfacial energies of the droplet to completely separate the polymer-stabilized inner core from the oil shell.

Surfactant Impact on Interfacial Protein Aggregation and Utilization of Surface Tension to Predict Surfactant Requirements for Biological Formulations.

Biological drug products are formulated with excipients to maintain stability over the shelf life of the product. Surfactants are added to the drug product to stabilize air-water interfaces known to induce protein aggregation. Early formulation development is focused on maintaining protein conformation and colloidal stability over the course of the drug product shelf life but rarely considers stability through dose preparation and administration.

Protease-Triggered, Integrin-Targeted Cellular Uptake of Recombinant Protein Micelles.

Targeting nanoparticles for drug delivery has great potential for improving efficacy and reducing side effects from systemic toxicity. New developments in the assembly of materials afford the opportunity to expose cryptic targeting domains in tissue-specific microenvironments in which certain proteases are expressed. Here, recombinant proteins are designed to combine the responsiveness to environmental proteases with specific targeting.

Interdisciplinary Rehabilitation Referrals in a Concussion Clinic Cohort: An Exploratory Analysis.

Objective: To assess the frequency and spectrum of referrals to rehabilitation disciplines in a concussion clinic population and factors associated with need for referral.

Design: Retrospective study.

Setting: Concussion clinic within the Physical Medicine and Rehabilitation Department of an academic medical center.

Caging metal ions with visible light-responsive nanopolymersomes.

Polymersomes are bilayer vesicles that self-assemble from amphiphilic diblock copolymers, and provide an attractive system for the delivery of biological and nonbiological molecules due to their environmental compatibility, mechanical stability, synthetic tunability, large aqueous core, and hyperthick hydrophobic membrane. Herein, we report a nanoscale photoresponsive polymersome system featuring a meso-to-meso ethyne-bridged bis[(porphinato)zinc] (PZn2) fluorophore hydrophobic membrane solute and dextran in the aqueous core. Upon 488 nm irradiation in solution or in microinjected zebrafish embryos, the polymersomes underwent deformation, as monitored by a characteristic red-shifted PZn2 emission spectrum and confirmed by cryo-TEM.

Superparamagnetic iron oxide nanoparticle micelles stabilized by recombinant oleosin for targeted magnetic resonance imaging.

Recombinant surfactants present a new platform for stabilizing and targeting nanoparticle imaging agents. Superparamagnetic iron oxide nanoparticle-loaded micelles for MRI contrast are stabilized by an engineered variant of the naturally occurring protein oleosin and targeted using a Her2/neu affibody-oleosin fusion. The recombinant oleosin platform allows simple targeting and the ability to easily swap the ligand for numerous targets.

Noncanonical self-assembly of highly asymmetric genetically encoded polypeptide amphiphiles into cylindrical micelles.

Elastin-like polypeptides (ELPs) are a class of biopolymers consisting of the pentameric repeat (VPGαG)n based on the sequence of mammalian tropoelastin that display a thermally induced soluble-to-insoluble phase transition in aqueous solution. We have discovered a remarkably simple approach to driving the spontaneous self-assembly of high molecular weight ELPs into nanostructures by genetically fusing a short 1.5 kDa (XGy)z assembly domain to one end of the ELP.

Recombinant protein-stabilized monodisperse microbubbles with tunable size using a valve-based microfluidic device.

Microbubbles are used as contrast enhancing agents in ultrasound sonography and more recently have shown great potential as theranostic agents that enable both diagnostics and therapy. Conventional production methods lead to highly polydisperse microbubbles, which compromise the effectiveness of ultrasound imaging and therapy. Stabilizing microbubbles with surfactant molecules that can impart functionality and properties that are desirable for specific applications would enhance the utility of microbubbles.

Spherical micelles assembled from variants of recombinant oleosin.

An emerging field in biomaterials is the creation and engineering of protein surfactants made by recombinant biotechnology. Protein surfactants made by recombinant biotechnology allow for complete control of the molecular weight and chemical sequence of the surfactant. The proteins are monodisperse in molecular weight, and functionalization with bioactive amino acid sequences is straightforwardly achieved through genetic engineering.

Modular synthesis of amphiphilic Janus glycodendrimers and their self-assembly into glycodendrimersomes and other complex architectures with bioactivity to biomedically relevant lectins.

The modular synthesis of 7 libraries containing 51 self-assembling amphiphilic Janus dendrimers with the monosaccharides D-mannose and D-galactose and the disaccharide D-lactose in their hydrophilic part is reported. These unprecedented sugar-containing dendrimers are named amphiphilic Janus glycodendrimers. Their self-assembly by simple injection of THF or ethanol solution into water or buffer and by hydration was analyzed by a combination of methods including dynamic light scattering, confocal microscopy, cryogenic transmission electron microscopy, Fourier transform analysis, and micropipet-aspiration experiments to assess mechanical properties.

Self-assembly of thermally responsive nanoparticles of a genetically encoded peptide polymer by drug conjugation.

Chimeric polypeptides (CPs) that are derived from elastin-like polypeptides (ELPs) can self-assemble to form nanoparticles by site-specific covalent attachment of hydrophobic molecules to one end of the biopolymer backbone. Molecules with a distribution coefficient greater than 1.5 impart sufficient amphiphilicity to drive self-assembly into sub-100 nm nanoparticles.

Self-assembly of tunable protein suprastructures from recombinant oleosin.

Using recombinant amphiphilic proteins to self-assemble suprastructures would allow precise control over surfactant chemistry and the facile incorporation of biological functionality. We used cryo-TEM to confirm self-assembled structures from recombinantly produced mutants of the naturally occurring sunflower protein, oleosin. We studied the phase behavior of protein self-assembly as a function of solution ionic strength and protein hydrophilic fraction, observing nanometric fibers, sheets, and vesicles.