A Phosphorylcholine Polymer Platform for Cancer Drug Delivery

Discusses the use of polymers to enhance a drug delivery system for breast cancer treatment. This presentation is part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer

Chemical Stabilization of Perovskite Solar Cells with Functional Fulleropyrrolidines.

While perovskite solar cells have invigorated the photovoltaic research community due to their excellent power conversion efficiencies (PCEs), these devices notably suffer from poor stability. To address this crucial issue, a solution-processable organic chemical inhibition layer (OCIL) was integrated into perovskite solar cells, resulting in improved device stability and a maximum PCE of 16.3%. Photoenhanced self-doping of the fulleropyrrolidine mixture in the interlayers afforded devices that were advantageously insensitive to OCIL thickness, ranging from 4 to 190 nm. X-ray photoelectron spectroscopy (XPS) indicated that the fulleropyrrolidine mixture improved device stability by stabilizing the metal electrode and trapping ionic defects (i.e., I-) that originate from the perovskite active layer. Moreover, degraded devices were rejuvenated by repeatedly peeling away and replacing the OCIL/Ag electrode, and this repeel and replace process resulted in further improvement to device stability with minimal variation of device efficiency

Process of forming crosslinked copolymer film, crosslinked copolymer film formed thereby, and water purification membrane

Azidoaryl-substituted cyclooctene monomers and synthesized and used in the preparation of various copolymers. Among these copolymers are those prepared from ring-opening metathesis polymerization of cyclooctene, polyethylene glycol-substituted cyclooctene, and azidoaryl-substituted cyclooctene. These copolymers are useful in the formation of crosslinked films that reduce fouling of water purification membranes.Board of Regents, University of Texas Syste

Sonodelivery in Skeletal Muscle: Current Approaches and Future Potential

There are currently multiple approaches to facilitate gene therapy via intramuscular gene delivery, such as electroporation, viral delivery, or direct DNA injection with or without polymeric carriers. Each of these methods has benefits, but each method also has shortcomings preventing it from being established as the ideal technique. A promising method, ultrasound-mediated gene delivery (or sonodelivery) is inexpensive, widely available, reusable, minimally invasive, and safe. Hurdles to utilizing sonodelivery include choosing from a large variety of conditions, which are often dependent on the equipment and/or research group, and moderate transfection efficiencies when compared to some other gene delivery methods. In this review, we provide a comprehensive look at the breadth of sonodelivery techniques for intramuscular gene delivery and suggest future directions for this continuously evolving field

Strain-stiffening gels based on latent crosslinking

Gels are an increasingly important class of soft materials with applications ranging from regenerative medicine to commodity materials. A major drawback of gels is their relative mechanical weakness, which worsens further under strain. We report a new class of responsive gels with latent crosslinking moieties that exhibit strain-stiffening behavior. This property results from the lability of disulfides, initially isolated in a protected state, then activated to crosslink on-demand. The active thiol groups are induced to form inter-chain crosslinks when subjected to mechanical compression, resulting in a gel that strengthens under strain. Molecular shielding design elements regulate the strain-sensitivity and spontaneous crosslinking tendencies of the polymer network. These strain-responsive gels represent a rational design of new advanced materials with on-demand stiffening properties with potential applications in elastomers, adhesives, foams, films, and fibers

Sonodelivery Facilitates Sustained Luciferase Expression from an Episomal Vector in Skeletal Muscle

Successful gene delivery to skeletal muscle is a desirable goal, not only for treating muscle diseases, but also for immunization, treatment of metabolic disorders, and/or delivering gene expression that can treat systemic conditions, such as bone metastatic cancer, for example. Although naked DNA uptake into skeletal muscle is possible, it is largely inefficient in the absence of additional chemical or physical delivery methods. We describe a system for delivery of non-viral or plasmid DNA to skeletal muscle using ultrasound-assisted sonoporation of a nanoplex combining plasmid DNA and a branched polymer based on poly(cyclooctene-graft-oligopeptide). The materials and methods described herein promise to advance the field of sonodelivery and of gene delivery to muscle for therapeutic applications since a simple system is presented that enables long-term gene expression in vivo with the promise of a minimal inflammatory gene expression profile

Functional Droplets that Recognize, Collect, and Transport Debris on Surfaces

We describe polymer-stabilized droplets capable of recognizing and picking up nanoparticles from substrates in experiments designed for transporting hydroxyapatite nanoparticles that represent the principal elemental composition of bone. Our experiments, which are inspired by cells that carry out materials transport in vivo, used oil-in-water droplets that traverse a nanoparticle-coated substrate driven by an imposed fluid flow. Nanoparticle capture is realized by interaction of the particles with chemical functionality embedded within the polymeric stabilizing layer on the droplets. Nanoparticle uptake efficiency is controlled by solution conditions and the extent of functionality available for contact with the nanoparticles. Moreover, in an elementary demonstration of nanoparticle transportation, particles retrieved initially from the substrate were later deposited “downstream,” illustrating a pickup and drop-off technique that represents a first step toward mimicking point-to-point transportation events conducted in living systems

Effect of Oligopeptide Orientation on Polymer-based DNA Delivery

Non-viral synthetic gene therapy reagents offer excellent structural and chemical versatility within non-immunogenic delivery systems, coupled with high therapeutic gene carrying capacity and long shelf life, making them attractive alternatives to viral systems. The success of non-viral transfection using polymers hinges on efficient nuclear uptake of nucleic acid cargo and overcoming intra- and extracellular barriers. This poster will describe the integration of the PKKKRKV heptapeptide (the Simian virus SV40 large T-antigen nuclear localization sequence, NLS) onto a polymer backbone, and the resultant high reporter gene expression in mice when administered by intramuscular ultrasound-mediated delivery. These novel polymers afforded protein expression higher than JetPEI™ in vivo, and in cell culture outperformed commercial reagents JetPEI™ and Lipofectamine 2000™, the latter being notorious for coupling high transfection efficiency with cytotoxicity. The orientation of the NLS peptide grafts relative to the polymer backbone markedly affected transfection performance both in vitro and in vivo. Quantitative polymerase chain reaction (qPCR) studies on transfected cells showed that polymers having the NLS attached at the valine residue afforded higher nuclear translocation, and subsequently higher protein expression, relative to those having the NLS groups attached in the opposite orientation. Besides nuclear uptake, the superior binding characteristics of these comb polymers compared to linear polylysine, as judged by atomistic and coarse grain simulations as well as polymer-DNA binding experiments, contributes to their enhanced transfection performance. Polyplexes formed from these comb polymer structures exhibit low cytotoxicity and high transfection efficiency both in vitro and in vivo, demonstrating the therapeutic promise of these novel gene therapy reagents

PEG-Phosphorylcholine Hydrogels As Tunable and Versatile Platforms for Mechanobiology

We report here the synthesis of a new class of hydrogels with an extremely wide range of mechanical properties suitable for cell studies. Mechanobiology has emerged as an important field in bioengineering, in part due to the development of synthetic polymer gels and fibrous protein biomaterials to control and quantify how cells sense and respond to mechanical forces in their microenvironment. To address the problem of limited availability of biomaterials, in terms of both mechanical range and optical clarity, we have prepared hydrogels that combine poly(ethylene glycol) (PEG) and phosphorylcholine (PC) zwitterions. Our goal was to create a hydrogel platform that exceeds the range of Young’s moduli reported for similar hydrogels, while being simple to synthesize and manipulate. The Young’s modulus of these “PEG-PC” hydrogels can be tuned over 4 orders of magnitude, much greater than commonly used hydrogels such as PEG-diacrylate, PEG-dimethacrylate, and polyacrylamide, with smaller average mesh sizes and optical clarity. We prepared PEG-PC hydrogels to study how substrate mechanical properties influence cell morphology, focal adhesion structure, and proliferation across multiple mammalian cell lines, as a proof of concept. These novel PEG-PC biomaterials represent a new and useful class of mechanically tunable hydrogels for mechanobiology