Chemical and Biomolecular Engineering - Research Publications
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ItemNanoengineering of Poly(ethylene glycol) Particles for Stealth and Targeting(AMER CHEMICAL SOC, 2018-09-18)The assembly of particles composed solely or mainly of poly(ethylene glycol) (PEG) is an emerging area that is gaining increasing interest within bio-nano science. PEG, widely considered to be the "gold standard" among polymers for drug delivery, is providing a platform for exploring fundamental questions and phenomena at the interface between particle engineering and biomedicine. These include the targeting and stealth behaviors of synthetic nanomaterials in biological environments. In this feature article, we discuss recent work in the nanoengineering of PEG particles and explore how they are enabling improved targeting and stealth performance. Specific examples include PEG particles prepared through surface-initiated polymerization, mesoporous silica replication via postinfiltration, and particle assembly through metal-phenolic coordination. This particle class exhibits unique in vivo behavior (e.g., biodistribution and immune cell interactions) and has recently been explored for drug delivery applications.
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ItemLigand-Functionalized Poly(ethylene glycol) Particles for Tumor Targeting and Intracellular Uptake.(American Chemical Society, 2019)Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g-1) when compared with the PEG (3% ID g-1) and PEG-RDG (7% ID g-1) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems.
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ItemConvective polymer assembly for the deposition of nanostructures and polymer thin films on immobilized particles(ROYAL SOC CHEMISTRY, 2014-11)We report the preparation of polymer particles via convective polymer assembly (CPA). Convection is used to move polymer solutions and cargo through an agarose gel that contains immobilized template particles. This method both coats and washes the particles in a process that is amenable to automation, and does not depend on passive diffusion or electrical currents, thus facilitating incorporation of fragile and nanoscale objects, such as liposomes and gold nanoparticles, into the thin polymer films. Template dissolution leads to the formation of stable polymer particles and capsules.
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ItemNanoengineering Particles through Template Assembly(AMER CHEMICAL SOC, 2017-01-10)
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ItemInnovation in Layer-by-Layer Assembly(AMER CHEMICAL SOC, 2016-12-14)Methods for depositing thin films are important in generating functional materials for diverse applications in a wide variety of fields. Over the last half-century, the layer-by-layer assembly of nanoscale films has received intense and growing interest. This has been fueled by innovation in the available materials and assembly technologies, as well as the film-characterization techniques. In this Review, we explore, discuss, and detail innovation in layer-by-layer assembly in terms of past and present developments, and we highlight how these might guide future advances. A particular focus is on conventional and early developments that have only recently regained interest in the layer-by-layer assembly field. We then review unconventional assemblies and approaches that have been gaining popularity, which include inorganic/organic hybrid materials, cells and tissues, and the use of stereocomplexation, patterning, and dip-pen lithography, to name a few. A relatively recent development is the use of layer-by-layer assembly materials and techniques to assemble films in a single continuous step. We name this "quasi"-layer-by-layer assembly and discuss the impacts and innovations surrounding this approach. Finally, the application of characterization methods to monitor and evaluate layer-by-layer assembly is discussed, as innovation in this area is often overlooked but is essential for development of the field. While we intend for this Review to be easily accessible and act as a guide to researchers new to layer-by-layer assembly, we also believe it will provide insight to current researchers in the field and help guide future developments and innovation.
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ItemInteractions between circulating nanoengineered polymer particles and extracellular matrix components in vitro(ROYAL SOC CHEMISTRY, 2017-02-01)The extracellular matrix (ECM) that surrounds cells in vivo represents a biological barrier for nanomaterials in biomedicine. Herein, we present a system for investigating the interactions between circulating polymer particles and ECM components in vitro using a commercially available flow-based device. We use this system to show how material-dependent interactions of two different particle types-one assembled using poly(ethylene glycol) (PEG) and one prepared using poly(methacrylic acid) (PMA)-affect their interactions with basement membrane extracts during in vitro circulation, with PEG particles remaining in circulation longer than PMA particles. Further, by comparing macroporous hyaluronic acid gel constructs (typically used for tissue engineering) with basement membrane extracts, we show that scaffold-effects (porosity and surface chemistry) impact on circulation time in vitro. The presented system is simple and modular, and can be used to rapidly screen fundamental interactions of engineered particles with biologically relevant microenvironments under flow-conditions.
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ItemDynamic Flow Impacts Cell-Particle Interactions: Sedimentation and Particle Shape Effects(AMER CHEMICAL SOC, 2016-10-25)The interaction of engineered particles with biological systems determines their performance in biomedical applications. Although standard static cell cultures remain the norm for in vitro studies, modern models mimicking aspects of the dynamic in vivo environment have been developed. Herein, we investigate fundamental cell-particle interactions under dynamic flow conditions using a simple and self-contained device together with standard multiwell cell culture plates. We engineer two particle systems and evaluate their cell interactions under dynamic flow, and we compare the results to standard static cell cultures. We find substantial differences between static and dynamic flow conditions and attribute these to particle shape and sedimentation effects. These results demonstrate how standard static assays can be complemented by dynamic flow assays for a more comprehensive understanding of fundamental cell-particle interactions.
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ItemSuper-Soft Hydrogel Particles with Tunable Elasticity in a Microfluidic Blood Capillary Model(WILEY-V C H VERLAG GMBH, 2014-11-19)Super-soft PEG hydrogel particles with tunable elasticity are prepared via a mesoporous silica templating method. The deformability behavior of these particles, in a microfluidic blood-capillary model, can be tailored to be similar to that of human red blood cells. These results provide a new platform for the design and development of soft hydrogel particles for investigating bio-nano interactions.
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ItemA Framework to Account for Sedimentation and Diffusion in Particle-Cell Interactions(AMER CHEMICAL SOC, 2016-11-29)In vitro experiments provide a solid basis for understanding the interactions between particles and biological systems. An important confounding variable for these studies is the difference between the amount of particles administered and that which reaches the surface of cells. Here, we engineer a hydrogel-based nanoparticle system and combine in situ characterization techniques, 3D-printed cell cultures, and computational modeling to evaluate and study particle-cell interactions of advanced particle systems. The framework presented demonstrates how sedimentation and diffusion can explain differences in particle-cell association, and provides a means to account for these effects. Finally, using in silico modeling, we predict the proportion of particles that reaches the cell surface using common experimental conditions for a wide range of inorganic and organic micro- and nanoparticles. This work can assist in the understanding and control of sedimentation and diffusion when investigating cellular interactions of engineered particles.
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ItemFluidized Bed Layer-by-Layer Microcapsule Formation(AMER CHEMICAL SOC, 2014-08-26)Polymer microcapsules can be used as bioreactors and artificial cells; however, preparation methods for cell-like microcapsules are typically time-consuming, low yielding, and/or involve custom microfluidics. Here, we introduce a rapid (∼30 min per batch, eight layers), scalable (up to 500 mg of templates), and efficient (98% yield) microcapsule preparation technique utilizing a fluidized bed for the layer-by-layer (LbL) assembly of polymers, and we investigate the parameters that govern the formation of robust capsules. Fluidization in water was possible for particles of comparable diameter to mammalian cells (>5 μm), with the experimental flow rates necessary for fluidization matching well with the theoretical values. Important variables for polymer film deposition and capsule formation were the concentration of polymer solution and the molecular weight of the polymer, while the volume of the polymer solution had a negligible impact. In combination, increasing the polymer molecular weight and polymer solution concentration resulted in improved film deposition and the formation of robust microcapsules. The resultant polymer microcapsules had a thickness of ∼5.5 nm per bilayer, which is in close agreement with conventionally prepared (quiescent (nonflow) adsorption/centrifugation/wash) LbL capsules. The technique reported herein provides a new way to rapidly generate microcapsules (approximately 8 times quicker than the conventional means), while being also amenable to scale-up and mass production.