Showing papers by "Stefan Zauscher published in 2018"
TL;DR: This work represents a fundamental advance in the generation of crosslinked biomaterials, especially in the form of soft matter colloids, and is one of the first demonstrations of successful use of UAAs in generating a novel material.
Abstract: Hydrogel particles are versatile materials that provide exquisite, tunable control over the sequestration and delivery of materials in pharmaceutics, tissue engineering, and photonics. The favorable properties of hydrogel particles depend largely on their size, and particles ranging from nanometers to micrometers are used in different applications. Previous studies have only successfully fabricated these particles in one specific size regime and required a variety of materials and fabrication methods. A simple yet powerful system is developed to easily tune the size of polypeptide-based, thermoresponsive hydrogel particles, from the nano- to microscale, using a single starting material. Particle size is controlled by the self-assembly and unique phase transition behavior of elastin-like polypeptides in bulk and within microfluidic-generated droplets. These particles are then stabilized through ultraviolet irradiation of a photo-crosslinkable unnatural amino acid (UAA) cotranslationally incorporated into the parent polypeptide. The thermoresponsive property of these particles provides an active mechanism for actuation and a dynamic responsive to the environment. This work represents a fundamental advance in the generation of crosslinked biomaterials, especially in the form of soft matter colloids, and is one of the first demonstrations of successful use of UAAs in generating a novel material.
51 citations
TL;DR: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells and the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy.
Abstract: Introduction Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. Material and methods In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core-shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-l-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-l-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. Results The spherical nanoparticles had an average size of 60-80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-l-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2-2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. Conclusion Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells.
43 citations
TL;DR: The preparation and characterization of photoresponsive hydrogels prepared by cross-linking of di-NHS ester of azobenzoic acid and four-armed, amine-terminated poly(ethylene glycol), and the effect of photoisomerization on the hydrogel structure are described to demonstrate the potential of these systems as reversible photoreSponsive biomaterials.
Abstract: Advances in biosensors and drug delivery are dependent on hydrogels that respond to external stimuli. In this work, we describe the preparation and characterization of photoresponsive hydrogels prepared by cross-linking of di-NHS ester of azobenzoic acid and four-armed, amine-terminated poly(ethylene glycol). The porous structure and composition of the hydrogels were confirmed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The reversible photoisomerization of the azobenzene-containing hydrogel cross-linkers in the gels was confirmed by absorption spectroscopy. Specifically, the photoisomerization of the cross-linkers between their trans and cis configurations was observed by monitoring the absorbance of the hydrogels at the two characteristic peaks of azobenzene (π-π* at 330 nm and n-π* at 435 nm). The effect of photoisomerization on the hydrogel structure was investigated by microscopy. Ultraviolet (UV) irradiation-induced reduction in hydrogel size was observed, which may be a result of the inherently smaller footprint of the cis azobenzene conformation, as well as dipole-dipole interactions between the polar cis azobenzene and the polymer network. The UV-triggered reduction in hydrogel size was accompanied by enhanced release of the near-infrared fluorescent dye Alexa Fluor 750 (AF750). Enhanced release of AF750 was observed in samples irradiated with UV versus dark control. Together, these data demonstrate the potential of these systems as reversible photoresponsive biomaterials.
40 citations
TL;DR: A class of silicone particles that addresses challenges for the encapsulation, protection and controlled release of retinol and other hydrophobic compounds and can encapsulate other AIs, including betamethasone, N, N‐diethyl‐meta‐toluamide (DEET), homosalate and ingenol mebutate are developed, establishing these particles as a true platform technology.
23 citations
TL;DR: Transition metal chalcogenide nanoparticles (NP) can be produced by a variety of microorganisms including bacteria, fungi, algae, and yeast, as well as cell-free approaches using enzymes as mentioned in this paper.
Abstract: Transition metal (TM) chalcogenides are a group of semiconductor materials with applications that range from antibacterial particles to thin films in energy conversion devices. Significant progress in synthetic biology combined with the benefits of low energy consumption and low toxic waste burden of “green synthesis,” have directed considerable research attention to the biosynthesis of these inorganic materials. TM chalcogenide nanoparticles (NP) can be produced by a variety of microorganisms including bacteria, fungi, algae, and yeast, as well as cell-free approaches using enzymes. Recent research shows that the size, crystal structure, and bandgap of these TM NPs can be well controlled, which has led to prototypical applications of these biosynthetic NPs in the areas of bio-remediation, bio-imaging, photocatalysis, and energy conversion. This review is the first to combine recent progress in the biosynthesis, property control, and applications of TM chalcogenide NPs.
23 citations
TL;DR: It is discovered that increasing the size and density of unnatural nucleobases enhances ssDNA resistance to degradation in the presence of exonuclease I, DNase I, and human serum, and this suggests that incorporating nucleobase-modified nucleotides into ssDNA, using enzymatic polymerization, is an easy and efficient strategy to prolong and tune the half-life of DNA-based materials in nucleases-containing environments.
16 citations
TL;DR: In this article, the authors review general mucin structure, recent trends in the design and synthesis of mucin mimics, and the ways mucin analogues can outperform native mucins.
Abstract: Mucins are a class of glycoproteins that serve key roles in tissue protection, hydration, and lubrication. However, their study and application are complicated by their post-translational modifications, heterogeneity, and their propensity to deteriorate upon isolation. As a result, several groups have made strides in synthesizing mucin-mimicking compounds for systematic study and therapeutic applications. In this paper, we review general mucin structure, recent trends in the design and synthesis of mucin mimics, and the ways mucin analogues can outperform native mucins. Specifically, we highlight the structures of lubricin and aggrecan, which are the subject of many biomimetic approaches. Furthermore, we showcase the structural features that allow analogues to mimic mucin functions and categorize them based on their roles as monolayer coatings, gel formers, or adhesion promoters. Lastly, we examine the chemical composition of mucin analogues, emphasizing how modular approaches provide flexibility to repurpose mucin mimics for different applications.
14 citations
TL;DR: The modular synthesis of protein-brush hybrids containing elastin-like polypeptides (ELP) as model proteins by copper-catalyzed azide-alkyne cycloaddition is reported, allowing for the synthesis ofprotein-bottlebrush hybrids with different proteins and brush polymers.
11 citations
TL;DR: It is demonstrated that genetic incorporation of a silica-binding peptide results in enhanced adsorption of these block copolymers onto silica surfaces as measured by quartz crystal microbalance and ellipsometry, and wettability measurements suggest that surface immobilization hampers the temperature-dependent conformational change of ELP micelles, while adsorbed ELP unimers retain their thermally responsive property at interfaces.
11 citations
TL;DR: The broader applicability of this novel urinary catheter prototype to remove fungal biofilms has been demonstrated, underscores the potential of mechanical disruption as a materials design strategy to combat fungal device-associated infections.
Abstract: Candida albicans is a leading cause of catheter-associated urinary tract infections and elimination of these biofilm-based infections without antifungal agents would constitute a significant medical advance. A novel urinary catheter prototype that utilizes on-demand surface deformation is effective at eliminating bacterial biofilms and here the broader applicability of this prototype to remove fungal biofilms has been demonstrated. C. albicans biofilms were debonded from prototypes by selectively inflating four additional intralumens surrounding the main lumen of the catheters to provide the necessary surface strain to remove the adhered biofilm. Deformable catheters eliminated significantly more biofilm than the controls (>90% eliminated vs 10% control; p < 0.001). Mechanical testing revealed that fungal biofilms have an elastic modulus of 45 ± 6.7 kPa with a fracture energy of 0.4-2 J m-2. This study underscores the potential of mechanical disruption as a materials design strategy to combat fungal device-associated infections.
6 citations
TL;DR: The authors exploit the ability of Escherichia coli to contribute to material fabrication by designing and optimizing growth platforms to direct inorganic nanoparticle (NP) synthesis, specifically cadmium sulfide (CdS) NPs, onto porous polycarbonate membranes.
Abstract: The emerging field of biofabrication capitalizes on nature's ability to create materials with a wide range of well-defined physical and electronic properties. Particularly, there is a current push to utilize programmed, self-organization of living cells for material fabrication. However, much research is still necessary at the interface of synthetic biology and materials engineering to make biofabrication a viable technique to develop functional devices. Here, the authors exploit the ability of Escherichia coli to contribute to material fabrication by designing and optimizing growth platforms to direct inorganic nanoparticle (NP) synthesis, specifically cadmium sulfide (CdS) NPs, onto porous polycarbonate membranes. Additionally, current, nonbiological, chemical synthesis methods for CdS NPs are typically energy intensive and use high concentrations of hazardous cadmium precursors. Using biosynthesis methods through microorganisms could potentially alleviate these issues by precipitating NPs with less energy and lower concentrations of toxic precursors. The authors adopted extracellular precipitation strategies to form CdS NPs on the membranes as bacterial/membrane composites and characterized them by spectroscopic and imaging methods, including energy dispersive spectroscopy, and scanning and transmission electron microscopy. This method allowed us to control the localization of NP precipitation throughout the layered bacterial/membrane composite, by varying the timing of the cadmium precursor addition. Additionally, the authors demonstrated the photodegradation of methyl orange using the CdS functionalized porous membranes, thus confirming the photocatalytic properties of these composites for eventual translation to device development. If combined with the genetically programmed self-organization of cells, this approach promises to directly pattern CdS nanostructures on solid supports.