Chemical and Biomolecular Engineering - Research Publications
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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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ItemNo Preview AvailableAn Enzyme-Coated Metal-Organic Framework Shell for Synthetically Adaptive Cell Survival(WILEY-V C H VERLAG GMBH, 2017-07-10)A bioactive synthetic porous shell was engineered to enable cells to survive in an oligotrophic environment. Eukaryotic cells (yeast) were firstly coated with a β-galactosidase (β-gal), before crystallization of a metal-organic framework (MOF) film on the enzyme coating; thereby producing a bioactive porous synthetic shell. The β-gal was an essential component of the bioactive shell as it generated nutrients (that is, glucose and galactose) required for cell viability in nutrient-deficient media (lactose-based). Additionally, the porous MOF coating carried out other vital functions, such as 1) shielding the cells from cytotoxic compounds and radiation, 2) protecting the non-native enzymes (β-gal in this instance) from degradation and internalization, and 3) allowing for the diffusion of molecules essential for the survival of the cells. Indeed, this bioactive porous shell enabled the survival of cells in simulated extreme oligotrophic environments for more than 7 days, leading to a decrease in cell viability less than 30 %, versus a 99 % decrease for naked yeast. When returned to optimal growth conditions the bioactive porous exoskeleton could be removed and the cells regained full growth immediately. The construction of bioactive coatings represents a conceptually new and promising approach for the next-generation of cell-based research and application, and is an alternative to synthetic biology or genetic modification.
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ItemOne-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering(AMER ASSOC ADVANCEMENT SCIENCE, 2013-07-12)The development of facile and versatile strategies for thin-film and particle engineering is of immense scientific interest. However, few methods can conformally coat substrates of different composition, size, shape, and structure. We report the one-step coating of various interfaces using coordination complexes of natural polyphenols and Fe(III) ions. Film formation is initiated by the adsorption of the polyphenol and directed by pH-dependent, multivalent coordination bonding. Aqueous deposition is performed on a range of planar as well as inorganic, organic, and biological particle templates, demonstrating an extremely rapid technique for producing structurally diverse, thin films and capsules that can disassemble. The ease, low cost, and scalability of the assembly process, combined with pH responsiveness and negligible cytotoxicity, makes these films potential candidates for biomedical and environmental applications.
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ItemPreparation of Nano- and Microcapsules by Electrophoretic Polymer Assembly(WILEY-V C H VERLAG GMBH, 2013)
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ItemInfluence of Ionic Strength on the Deposition of Metal-Phenolic Networks(AMER CHEMICAL SOC, 2017-10-10)Metal-phenolic networks (MPNs) are a versatile class of self-assembled materials that are able to form functional thin films on various substrates with potential applications in areas including drug delivery and catalysis. Different metal ions (e.g., FeIII, CuII) and phenols (e.g., tannic acid, gallic acid) have been investigated for MPN film assembly; however, a mechanistic understanding of the thermodynamics governing MPN formation remains largely unexplored. To date, MPNs have been deposited at low ionic strengths (<5 mM), resulting in films with typical thicknesses of ∼10 nm, and it is still unclear how a bulk complexation reaction results in homogeneous thin films when a substrate is present. Herein we explore the influence of ionic strength (0-2 M NaCl) on the conformation of MPN precursors in solution and how this determines the final thickness and morphology of MPN films. Specifically, the film thickness increases from 10 nm in 0 M NaCl to 12 nm in 0.5 M NaCl and 15 nm in 1 M NaCl, after which the films grow rougher rather than thicker. For example, the root-mean-square roughness values of the films are constant below 1 M NaCl at 1.5 nm; in contrast, the roughness is 3 nm at 1 M NaCl and increases to 5 nm at 2 M NaCl. Small-angle X-ray scattering and molecular dynamics simulations allow for comparisons to be made with chelated metals and polyelectrolyte thin films. For example, at a higher ionic strength (2 M NaCl), sodium ions shield the galloyl groups of tannic acid, allowing them to extend away from the FeIII center and interact with other MPN complexes in solution to form thicker and rougher films. As the properties of films determine their final performance and application, the ability to tune both thickness and roughness using salts may allow for new applications of MPNs.
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ItemSelf-Assembled Nanoparticles from Phenolic Derivatives for Cancer Therapy(WILEY, 2017-08-23)Therapeutic nanoparticles hold clinical promise for cancer treatment by avoiding limitations of conventional pharmaceuticals. Herein, a facile and rapid method is introduced to assemble poly(ethylene glycol) (PEG)-modified Pt prodrug nanocomplexes through metal-polyphenol complexation and combined with emulsification, which results in ≈100 nm diameter nanoparticles (PtP NPs) that exhibit high drug loading (0.15 fg Pt per nanoparticle) and low fouling properties. The PtP NPs are characterized for potential use as cancer therapeutics. Mass cytometry is used to quantify uptake of the nanoparticles and the drug concentration in individual cells in vitro. The PtP NPs have long circulation times, with an elimination half-life of ≈18 h in healthy mice. The in vivo antitumor activity of the PtP NPs is systematically investigated in a human prostate cancer xenograft mouse model. Mice treated with the PtP NPs demonstrate four times better inhibition of tumor growth than either free prodrug or cisplatin. This study presents a promising strategy to prepare therapeutic nanoparticles for biomedical applications.
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ItemPolymer Capsules for Plaque-Targeted In Vivo Delivery (vol 28, pg 7703, 2016)(WILEY-V C H VERLAG GMBH, 2016-09-28)
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ItemNo Preview AvailableMetal-Organic Frameworks: Biomimetic Replication of Microscopic Metal-Organic Framework Patterns Using Printed Protein Patterns (Adv. Mater. 45/2015).(Wiley, 2015-12)K. Liang, P. Falcaro, and co-workers report on page 7293 that metal-organic frameworks (MOFs) can be replicated in a biomimetic fashion from protein patterns on a surface. Bendable, fluorescent MOF patterns are formed with micrometer resolution under ambient conditions. This technique is used to grow MOF patterns from fingerprint residue in 30 s with high fidelity. This technique is not only relevant for crime-scene investigation, but also for biomedical applications.
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ItemImmersive Polymer Assembly on Immobilized Particles for Automated Capsule Preparation(WILEY-V C H VERLAG GMBH, 2013-12)We report a versatile approach for polymer capsule preparation using immobilized particles, which are immersed into polymer solutions either manually or by using an automated robotic dipping machine. This technique produces polyelectrolyte capsules with improved retention over conventionally prepared capsules. Additionally, responsive hydrogel capsules of different diameter can be prepared simultaneously.
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ItemPeptide-Tunable Drug Cytotoxicity via One-Step Assembled Polymer Nanoparticles(WILEY-V C H VERLAG GMBH, 2014-04)A novel class of nanoparticles is developed for the co-delivery of a short cell penetrating peptide and a chemotherapeutic drug to achieve enhanced cytotoxicity. Tunable cytotoxicity is achieved through non-toxic peptide-facilitated gating. The strategy relies on a one-step blending process from polymer building blocks to form monodisperse, PEGylated particles that are sensitive to cellular pH variations. By varying the amount of peptide loading, the chemotherapeutic effects can be enhanced by up to 30-fold.