Publications by authors named "Alshakim Nelson"

43 Publications

Bioproduced Proteins On Demand (Bio-POD) in hydrogels using .

Bioact Mater 2021 Aug 27;6(8):2390-2399. Epub 2021 Jan 27.

Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.

Traditional production of industrial and therapeutic proteins by eukaryotic cells typically requires large-scale fermentation capacity. As a result, these systems are not easily portable or reusable for on-demand protein production applications. In this study, we employ Bioproduced Proteins On Demand (Bio-POD), a F127-bisurethane methacrylate hydrogel-based technique that immobilizes engineered for preservable, on-demand production and secretion of medium- and high-molecular weight proteins (in this case, SEAP, α-amylase, and anti-HER2). The gel samples containing encapsulated-yeast demonstrated sustained protein production and exhibited productivity immediately after lyophilization and rehydration. The hydrogel platform described here is the first hydrogel immobilization using a system to produce recombinant proteins of this breadth. These results highlight the potential of this formulation to establish a cost-effective bioprocessing strategy for on-demand protein production.
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http://dx.doi.org/10.1016/j.bioactmat.2021.01.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846901PMC
August 2021

3D bioprinting of mechanically tuned bioinks derived from cardiac decellularized extracellular matrix.

Acta Biomater 2021 01 7;119:75-88. Epub 2020 Nov 7.

Department of Bioengineering, University of Washington, Seattle, WA 98195, United States; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, United States; Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States. Electronic address:

3D bioprinting is a powerful technique for engineering tissues used to study cell behavior and tissue properties in vitro. With the right formulation and printing parameters, bioinks can provide native biological and mechanical cues while allowing for versatile 3D structures that recapitulate tissue-level organization. Bio-based materials that support cellular adhesion, differentiation, and proliferation - including gelatin, collagen, hyaluronic acid, and alginate - have been successfully used as bioinks. In particular, decellularized extracellular matrix (dECM) has become a promising material with the unique ability to maintain both biochemical and topographical micro-environments of native tissues. However, dECM has shown technical limitations for 3D printing (3DP) applications posed by its intrinsically low mechanical stability. Herein, we report hydrogel bioinks composed of partially digested, porcine cardiac decellularized extracellular matrix (cdECM), Laponite-XLG nanoclay, and poly(ethylene glycol)-diacrylate (PEG-DA). The Laponite facilitated extrusion-based 3DP, while PEG-DA enabled photo-polymerization after printing. Improving upon previously reported bioinks derived from dECM, our bioinks combine extrudability, shape fidelity, rapid cross-linking, and cytocompatibility in a single formulation (> 97% viability of encapsulated human cardiac fibroblasts and > 94% viability of human induced pluripotent stem cell derived cardiomyocytes after 7 days). The compressive modulus of the cured hydrogel bioinks was tunable from 13.4-89 kPa by changing the concentration of PEG-DA in the bioink formulation. Importantly, this span of mechanical stiffness encompasses ranges of tissue stiffness from healthy (compressive modulus ~5-15 kPa) to fibrotic (compressive modulus ~30-100 kPa) cardiac tissue states. The printed constructs demonstrated shape fidelity, adaptability to different printing conditions, and high cell viability following extrusion and photo-polymerization, highlighting the potential for applications in modeling both healthy and fibrotic cardiac tissue.
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http://dx.doi.org/10.1016/j.actbio.2020.11.006DOI Listing
January 2021

Physical Confinement Impacts Cellular Phenotypes within Living Materials.

ACS Appl Bio Mater 2020 Jul 7;3(7):4273-4281. Epub 2020 Jun 7.

Institute of Technology, University of Tartu, 50411 Tartu, Estonia.

Additive manufacturing allows three-dimensional printing of polymeric materials together with cells, creating living materials for applications in biomedical research and biotechnology. However, an understanding of the cellular phenotype within living materials is lacking, which is a key limitation for their wider application. Herein, we present an approach to characterize the cellular phenotype within living materials. We immobilized the budding yeast in three different photo-cross-linkable triblock polymeric hydrogels containing F127-bis-urethane methacrylate, F127-dimethacrylate, or poly(alkyl glycidyl ether)-dimethacrylate. Using optical and scanning electron microscopy, we showed that hydrogels based on these polymers were stable under physiological conditions, but yeast colonies showed differences in the interaction within the living materials. We found that the physical confinement, imparted by compositional and structural properties of the hydrogels, impacted the cellular phenotype by reducing the size of cells in living materials compared with suspension cells. These properties also contributed to the differences in immobilization patterns, growth of colonies, and colony coatings. We observed that a composition-dependent degradation of polymers was likely possible by cells residing in the living materials. In conclusion, our investigation highlights the need for a holistic understanding of the cellular response within hydrogels to facilitate the synthesis of application-specific polymers and the design of advanced living materials in the future.
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http://dx.doi.org/10.1021/acsabm.0c00335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375193PMC
July 2020

Cell-Laden Hydrogels for Multikingdom 3D Printing.

Macromol Biosci 2020 08 22;20(8):e2000121. Epub 2020 Jun 22.

Department of Chemistry, University of Washington, Box 351700, Seattle, WA, 98195-1700, USA.

Living materials are created through the embedding of live, whole cells into a matrix that can house and sustain the viability of the encapsulated cells. Through the immobilization of these cells, their bioactivity can be harnessed for applications such as bioreactors for the production of high-value chemicals. While the interest in living materials is growing, many existing materials lack robust structure and are difficult to pattern. Furthermore, many living materials employ only one type of microorganism, or microbial consortia with little control over the arrangement of the various cell types. In this work, a Pluronic F127-based hydrogel system is characterized for the encapsulation of algae, yeast, and bacteria to create living materials. This hydrogel system is also demonstrated to be an excellent material for additive manufacturing in the form of direct write 3D-printing to spatially arrange the cells within a single printed construct. These living materials allow for the development of incredibly complex, immobilized consortia, and the results detailed herein further enhance the understanding of how cells behave within living material matrices. The utilization of these materials allows for interesting applications of multikingdom microbial cultures in immobilized bioreactor or biosensing technologies.
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http://dx.doi.org/10.1002/mabi.202000121DOI Listing
August 2020

Compartmentalized microbes and co-cultures in hydrogels for on-demand bioproduction and preservation.

Nat Commun 2020 02 4;11(1):563. Epub 2020 Feb 4.

Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.

Most mono- and co-culture bioprocess applications rely on large-scale suspension fermentation technologies that are not easily portable, reusable, or suitable for on-demand production. Here, we describe a hydrogel system for harnessing the bioactivity of embedded microbes for on-demand small molecule and peptide production in microbial mono-culture and consortia. This platform bypasses the challenges of engineering a multi-organism consortia by utilizing a temperature-responsive, shear-thinning hydrogel to compartmentalize organisms into polymeric hydrogels that control the final consortium composition and dynamics without the need for synthetic control of mutualism. We demonstrate that these hydrogels provide protection from preservation techniques (including lyophilization) and can sustain metabolic function for over 1 year of repeated use. This approach was utilized for the production of four chemical compounds, a peptide antibiotic, and carbohydrate catabolism by using either mono-cultures or co-cultures. The printed microbe-laden hydrogel constructs' efficiency in repeated production phases, both pre- and post-preservation, outperforms liquid culture.
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http://dx.doi.org/10.1038/s41467-020-14371-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000784PMC
February 2020

Additive Manufacturing of Bovine Serum Albumin-Based Hydrogels and Bioplastics.

Biomacromolecules 2020 02 27;21(2):484-492. Epub 2019 Nov 27.

Department of Chemistry , University of Washington , Seattle , Washington 98195 , United States.

Biosourced and biodegradable polymers for additive manufacturing could enable the rapid fabrication of parts for a broad spectrum of applications ranging from healthcare to aerospace. However, a limited number of these materials are suitable for vat photopolymerization processes. Herein, we report a two-step additive manufacturing process to fabricate robust protein-based constructs using a commercially available laser-based stereolithography printer. Methacrylated bovine serum albumin (MA-BSA) was synthesized and formulated into aqueous resins that were used to print complex three-dimensional (3D) objects with a resolution comparable to a commercially available resin. The MA-BSA resins were characterized by rheometry to determine the viscosity and the cure rate, as both parameters can ultimately be used to predict the printability of the resin. In the first step of patterning these materials, the MA-BSA resin was 3D printed, and in the second step, the printed construct was thermally cured to denature the globular protein and increase the intermolecular noncovalent interactions. Thus, the final 3D printed part was comprised of both chemical and physical cross-links. Compression studies of hydrated and dehydrated constructs demonstrated a broad range of compressive strengths and Young's moduli that could be further modulated by adjusting the type and amount of co-monomer. The printed hydrogel constructs demonstrated good cell viability (>95%) after a 21 day culture period. These MA-BSA resins are expected to be compatible with other vat photopolymerization techniques including digital light projection and continuous liquid interface production.
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http://dx.doi.org/10.1021/acs.biomac.9b01236DOI Listing
February 2020

Poly(alkyl glycidyl ether) hydrogels for harnessing the bioactivity of engineered microbes.

Faraday Discuss 2019 10;219(0):58-72

Department of Chemistry, University of Washington, Seattle, WA 98195, USA.

Herein, we describe a method to produce yeast-laden hydrogel inks for the direct-write 3D printing of cuboidal lattices for immobilized whole-cell catalysis. A poly(alkyl glycidyl ether)-based triblock copolymer was designed to have three important features for this application: (1) a temperature response, which allowed for facile processing of the material; (2) a shear response, which facilitated the extrusion of the material through a nozzle; and (3) UV light induced polymerization, which enabled the post-extrusion chemical crosslinking of network chains, and the fabrication of robust printed objects. These three key stimuli responses were confirmed via rheometrical characterization. A genetically-engineered yeast strain with an upregulated α-factor production pathway was incorporated into the hydrogel ink and 3D printed. The immobilized yeast cells exhibited adequate viability of 87.5% within the hydrogel. The production of the upregulated α-factor was detected using a detecting yeast strain and quantified at 268 nM (s = 34.6 nM) over 72 h. The reusability of these bioreactors was demonstrated via immersion of the yeast-laden hydrogel lattice in fresh SC media and confirmed by the detection of similar amounts of upregulated α-factor at 259 nM (s = 45.1 nM). These yeast-laden materials represent an attractive opportunity for whole-cell catalysis of other high-value products in a sustainable and continuous manner.
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http://dx.doi.org/10.1039/c9fd00019dDOI Listing
October 2019

3D printed coaxial nozzles for the extrusion of hydrogel tubes toward modeling vascular endothelium.

Biofabrication 2019 07 12;11(4):045009. Epub 2019 Jul 12.

Department of Chemistry, University of Washington, Seattle, WA, United States of America.

Engineered tubular constructs made from soft biomaterials are employed in a myriad of applications in biomedical science. Potential uses of these constructs range from vascular grafts to conduits for enabling perfusion of engineered tissues and organs. The fabrication of standalone tubes or complex perfusable constructs from biofunctional materials, including hydrogels, via rapid and readily accessible routes is desirable. Here we report a methodology in which customized coaxial nozzles are 3D printed using commercially available stereolithography (SLA) 3D printers. These nozzles can be used for the fabrication of hydrogel tubes via coextrusion of two shear-thinning hydrogels: an unmodified Pluronic F-127 (F127) hydrogel and an F127-bisurethane methacrylate (F127-BUM) hydrogel. We demonstrate that different nozzle geometries can be modeled via computer-aided design and 3D printed in order to generate tubes or coaxial filaments with different cross-sectional geometries. We were able to fabricate tubes with luminal diameters or wall thicknesses as small as ∼150 μm. Finally, we show that these tubes can be functionalized with collagen I to enable cell adhesion, and human umbilical vein endothelial cells can be cultured on the luminal surfaces of these tubes to yield tubular endothelial monolayers. Our approach could enable the rapid fabrication of biofunctional hydrogel conduits which can ultimately be utilized for engineering in vitro models of tubular biological structures.
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http://dx.doi.org/10.1088/1758-5090/ab2b4dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350911PMC
July 2019

Additive Manufacturing of Catalytically Active Living Materials.

ACS Appl Mater Interfaces 2018 Apr 10;10(16):13373-13380. Epub 2018 Apr 10.

Department of Chemistry , University of Washington , Box 351700, Seattle , Washington 98195 , United States.

Living materials, which are composites of living cells residing in a polymeric matrix, are designed to utilize the innate functionalities of the cells to address a broad range of applications such as fermentation and biosensing. Herein, we demonstrate the additive manufacturing of catalytically active living materials (AMCALM) for continuous fermentation. A multi-stimuli-responsive yeast-laden hydrogel ink, based on F127-dimethacrylate, was developed and printed using a direct-write 3D printer. The reversible stimuli-responsive behaviors of the polymer hydrogel inks to temperature and pressure are critical, as they enabled the facile incorporation of yeast cells and subsequent fabrication of 3D lattice constructs. Subsequent photo-cross-linking of the printed polymer hydrogel afforded a robust elastic material. These yeast-laden living materials were metabolically active in the fermentation of glucose into ethanol for 2 weeks in a continuous batch process without significant reduction in efficiency (∼90% yield of ethanol). This cell immobilization platform may potentially be applicable toward other genetically modified yeast strains to produce other high-value chemicals in a continuous biofermentation process.
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http://dx.doi.org/10.1021/acsami.8b02719DOI Listing
April 2018

Catalytically Initiated Gel-in-Gel Printing of Composite Hydrogels.

ACS Appl Mater Interfaces 2017 Nov 9;9(46):40898-40904. Epub 2017 Nov 9.

Department of Chemistry, University of Washington , Seattle, Washington 98195, United States.

Herein, we describe a method to 3D print robust hydrogels and hydrogel composites via gel-in-gel 3D printing with catalytically activated polymerization to induce cross-linking. A polymerizable shear-thinning hydrogel ink with tetramethylethylenediamine as catalyst was directly extruded into a shear-thinning hydrogel support bath with ammonium persulfate as initiator in a pattern-wise manner. When the two gels came into contact, the free radicals generated by the catalyst initiated the free-radical polymerization of the hydrogel ink. Unlike photocuring, a catalyst-initiated polymerization is suitable for printing hydrogel composites of varying opacity, since it does not depend upon light penetration through the sample. The hydrogel support bath also exhibited a temperature-responsive behavior in which the gel "melted" upon cooling below 16 °C. Therefore, the printed object was easily removed by cooling the gel to a liquid state. Hydrogel composites with graphene oxide and multiwalled carbon nanotubes (MWCNTs) were successfully printed. The printed composites with MWCNTs afforded photothermally active objects, which have utility as stimuli-responsive actuators.
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http://dx.doi.org/10.1021/acsami.7b14177DOI Listing
November 2017

Developments in Dynamic Covalent Chemistries from the Reaction of Thiols with Hexahydrotriazines.

J Am Chem Soc 2015 Nov 4;137(45):14248-51. Epub 2015 Nov 4.

IBM Almaden Research Center , San Jose, California 95120, United States.

Dynamic covalent chemistries have garnered significant attention for their potential to revolutionize technologies in the material fields (engineering, biomedical, and sensors) and synthetic design strategies as they provide access to stimuli responsiveness and adaptive behaviors. However, only a limited number of molecular motifs have been known to display this dynamic behavior under mild conditions. Here, we identified a dynamic covalent motif-thioaminals-that is produced from the reaction of hexahydrotriazines (HTs) with thiols. Furthermore, we report on the synthesis of a new family of step-growth polymers based on this motif. The condensation efficiently proceeds to quantitative yields within a short time frame and offers versatility in functional group tolerance; thus, it can be exploited to synthesize both small molecule thioaminals as well as high molecular weight polymers from the step-growth polymerization of HTs with dithiols. Careful evaluation of substituted HTs and organic thiols supported by DFT calculations led to a chemically diverse library of polymers based on this motif. Finally, dynamic substitution reactions were employed toward the facile preparation of functional oligomers and macromolecules. This dynamic covalent motif is particularly attractive for a range of applications that include material design and drug delivery due to the economic feasibility of synthesis.
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http://dx.doi.org/10.1021/jacs.5b08815DOI Listing
November 2015

Monolayer assembly of ferrimagnetic Co(x)Fe(3-x)O4 nanocubes for magnetic recording.

Nano Lett 2014 Jun 9;14(6):3395-9. Epub 2014 May 9.

Department of Chemistry, Brown University , Providence, Rhode Island 02912, United States.

We report a facile synthesis of monodisperse ferrimagnetic Co(x)Fe(3-x)O4 nanocubes (NCs) through thermal decomposition of Fe(acac)3 and Co(acac)2 (acac = acetylacetonate) in the presence of oleic acid and sodium oleate. The sizes of the NCs are tuned from 10 to 60 nm, and their composition is optimized at x = 0.6 to show strong ferrimagnetism with the 20 nm Co0.6Fe2.4O4 NCs showing a room temperature Hc of 1930 Oe. The ferrimagnetic NCs are self-assembled at the water-air interface into a large-area (in square centimeter) monolayer array with a high packing density and (100) texture. The 20 nm NC array can be recorded at linear densities ranging from 254 to 31 kfci (thousand flux changes per inch). The work demonstrates the great potential of solution-phase synthesis and self-assembly of magnetic array for magnetic recording applications.
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http://dx.doi.org/10.1021/nl500904aDOI Listing
June 2014

Supramolecular high-aspect ratio assemblies with strong antifungal activity.

Nat Commun 2013 ;4:2861

1] IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, USA [2] Department of Polymer Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan [3].

Efficient and pathogen-specific antifungal agents are required to mitigate drug resistance problems. Here we present cationic small molecules that exhibit excellent microbial selectivity with minimal host toxicity. Unlike typical cationic polymers possessing molecular weight distributions, these compounds have an absolute molecular weight aiding in isolation and characterization. However, their specific molecular recognition motif (terephthalamide-bisurea) facilitates spontaneous supramolecular self-assembly manifesting in several polymer-like properties. Computational modelling of the terephthalamide-bisurea structures predicts zig-zag or bent arrangements where distal benzyl urea groups stabilize the high-aspect ratio aqueous supramolecular assemblies. These nanostructures are confirmed by transmission electron microscopy and atomic force microscopy. Antifungal activity against drug-sensitive and drug-resistant strains with in vitro and in vivo biocompatibility is observed. Additionally, despite repeated sub-lethal exposures, drug resistance is not induced. Comparison with clinically used amphotericin B shows similar antifungal behaviour without any significant toxicity in a C. albicans biofilm-induced mouse keratitis model.
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http://dx.doi.org/10.1038/ncomms3861DOI Listing
October 2014

Programmable nanoparticle ensembles via high-throughput directed self-assembly.

Langmuir 2013 Mar 4;29(11):3567-74. Epub 2013 Mar 4.

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, USA.

We present a simple and facile strategy for the directed self-assembly of nanoparticles into complex geometries using a minimal set of post guiding features patterned on a substrate. This understanding is based on extensive studies of nanoparticle self-assembly into linear, dense-packed, circular, and star-shaped ensembles when coated onto patterned substrates of predefined post arrays. We determined the conditions under which nanoparticles assemble and "connect" two adjacent post features, thereby forming the desired shapes. We demonstrate that with rational design of the post patterns to enforce the required pairwise interactions with posts, we can create arbitrary arrangements of nanoparticles-for example, to write "IBM" in a deterministic manner. This demonstration of programmable, high-throughput directed self-assembly of nanoparticles shows an alternative route to generate functional nanoparticle assemblies.
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http://dx.doi.org/10.1021/la4000457DOI Listing
March 2013

High-throughput directed self-assembly of core-shell ferrimagnetic nanoparticle arrays.

Langmuir 2013 Jun 31;29(24):7472-7. Epub 2013 Jan 31.

IBM Almaden Research Center, San Jose, California 95120, United States.

Magnetic nanoparticles (MNPs) provide a set of building blocks for constructing stimuli-responsive nanoscale materials with properties that are unique to this scale. The size and the composition of MNPs are tunable to meet the requirements for a range of applications including biosensors and data storage. Although many of these technologies would significantly benefit from the organization of nanoparticles into higher-order architectures, the precise placement and arrangement of nanoparticles over large areas of a surface remain a challenge. Herein, we demonstrate the viability of magnetic nanoparticles for patterned recording media utilizing a template-directed self-assembly process to afford well-defined nanostructures of magnetic nanoparticles and access these assemblies using magnetic force microscopy and a magnetic recording head. Photolithographically defined holes were utilized as templates to form assemblies of ferrimagnetic nanoparticle rings or pillars selectively over a large area (>1 cm(2)) in just 30 s. This approach is applicable to other nanoparticle systems as well and enables their high-throughput self-assembly for future advanced device fabrication.
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http://dx.doi.org/10.1021/la304573pDOI Listing
June 2013

Broad-spectrum antimicrobial supramolecular assemblies with distinctive size and shape.

ACS Nano 2012 Oct 1;6(10):9191-9. Epub 2012 Oct 1.

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, USA.

With the increased prevalence of antibiotic-resistant infections, there is an urgent need for innovative antimicrobial treatments. One such area being actively explored is the use of self-assembling cationic polymers. This relatively new class of materials was inspired by biologically pervasive cationic host defense peptides. The antimicrobial action of both the synthetic polymers and naturally occurring peptides is believed to be complemented by their three-dimensional structure. In an effort to evaluate shape effects on antimicrobial materials, triblock polymers were polymerized from an assembly directing terephthalamide-bisurea core. Simple changes to this core, such as the addition of a methylene spacer, served to direct self-assembly into distinct morphologies-spheres and rods. Computational modeling also demonstrated how subtle core changes could directly alter urea stacking motifs manifesting in unique multidirectional hydrogen-bond networks despite the vast majority of material consisting of poly(lactide) (interior block) and cationic polycarbonates (exterior block). Upon testing the spherical and rod-like morphologies for antimicrobial properties, it was found that both possessed broad-spectrum activity (Gram-negative and Gram-positive bacteria as well as fungi) with minimal hemolysis, although only the rod-like assemblies were effective against Candida albicans.
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http://dx.doi.org/10.1021/nn3035217DOI Listing
October 2012

Delivery of anticancer drugs using polymeric micelles stabilized by hydrogen-bonding urea groups.

Macromol Rapid Commun 2010 Jul 22;31(13):1187-92. Epub 2010 Jun 22.

Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.

Polymeric micelles comprising a hydrogen-bonding core were formed from block copolymers with pendant urea groups and explored as drug delivery vehicles. The amphiphilic block copolymers were synthesized by organocatalytic ring opening polymerization (ROP) of urea-functionalized cyclic carbonates from a poly(ethylene glycol) macroinitiator. The urea functionality was incorporated because its ability to increase the hydrophobic core's affinity toward polar organic compounds through intermolecular hydrogen bonding. Doxorubicin (DOX), a lipophilic anticancer drug with hydrogen-bonding functionalities, was systematically incorporated into the micelle's hydrophobic interior via hydrogen bonding to the functionalized monomers. Micelles employing urea groups were found to more efficiently interact with DOX thus allowing increased drug loading capacity while maintaining a desirable micellular size. More importantly, while DOX-loaded micelles were shown to kill HepG2 human liver carcinoma cell lines efficiently, all of the polymers were non-cytotoxic.
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http://dx.doi.org/10.1002/marc.201000105DOI Listing
July 2010

Monodisperse cobalt ferrite nanomagnets with uniform silica coatings.

Langmuir 2010 Nov 20;26(22):17546-51. Epub 2010 Oct 20.

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, United States.

Ferro- and ferrimagnetic nanoparticles are difficult to manipulate in solution as a consequence of the formation of magnetically induced nanoparticle aggregates, which hamper the utility of these particles for applications ranging from data storage to bionanotechnology. Nonmagnetic shells that encapsulate these magnetic particles can reduce the interparticle magnetic interactions and improve the dispersibility of the nanoparticles in solution. A route to create uniform silica shells around individual cobalt ferrite nanoparticles--which uses poly(acrylic acid) to bind to the nanoparticle surface and inhibit nanoparticle aggregation prior to the addition of a silica precursor--was developed. In the absence of the poly(acrylic acid) the cobalt ferrite nanoparticles irreversibly aggregated during the silica shell formation. The thickness of the silica shell around the core-shell nanoparticles could be controlled in order to tune the interparticle magnetic coupling as well as inhibit magnetically induced nanoparticle aggregation. These ferrimagnetic core-silica shell structures form stable dispersion in polar solvents such as EtOH and water, which is critical for enabling technologies that require the assembly or derivatization of ferrimagnetic particles in solution.
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http://dx.doi.org/10.1021/la103042qDOI Listing
November 2010

A simple and efficient synthesis of functionalized cyclic carbonate monomers using a versatile pentafluorophenyl ester intermediate.

J Am Chem Soc 2010 Oct;132(42):14724-6

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, United States.

An improved two-step synthetic route to functionalized cyclic carbonate monomers that features a novel cyclic carbonate intermediate with an active pentafluorophenyl ester group (MTC-OPhF(5)) has been developed. The versatile pentafluorophenyl ester intermediate can be synthesized on the gram to kilogram scale in one high-yielding step and is easy to store and handle on the benchtop. The active pentafluorophenyl ester of MTC-OPhF(5) is amenable to further substitution with suitable nucleophiles such as alcohols and amines to generate functionalized cyclic carbonates in high yields. The substitution reaction is tolerant of a wide variety of functionalities, including various hydrophobic and hydrophilic groups, reactive functionalities (via thiol-ene click chemistry or alkyl halides), and protected acids, alcohols, thiols, and amines. In view of the ever-increasing need for biodegradable and biocompatible polymers, this new methodology provides a simple and versatile platform for the synthesis of new and innovative materials.
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http://dx.doi.org/10.1021/ja105332kDOI Listing
October 2010

Hydrogen bonding-enhanced micelle assemblies for drug delivery.

Biomaterials 2010 Nov 11;31(31):8063-71. Epub 2010 Aug 11.

IBM Almaden Research Center, 650 Harry Road, San Jose, CA 95120, USA.

Ring-opening polymerization (ROP) of functionalized cyclic carbonates derived from 2,2-bis(methylol)propionic acid (bis-MPA) allows for incorporation of H-bonding urea-functional groups into block copolymers with a potential application of supramolecular drug-delivery systems. The strong H-bonding functionalities of poly(ethylene glycol)-block-poly(ethyl-random-urea carbonate) (PEG-P(E(1-x)-U(x))C) block copolymers not only lowered critical micelles concentration (cmc) of the block copolymer (to 1/4x) in aqueous environment compared to conventional PEG-poly(trimethylene carbonate) (PEG-PTMC) block copolymer without the non-covalent stabilization, but also improved kinetic stability of micelles and Dox-loaded micelles in the presence of a destabilizing agent. It was observed that the incorporation of anticancer drug doxorubicin affected the micellization process of block copolymers in water and caused a sudden increase in sizes of drug-loaded micelles above 200 nm. This phenomenon that can be a significant drawback in drug delivery applications was considerably mitigated in urea-bearing block copolymer/Dox micelles with simultaneously accompanying a significant improvement in drug loading. In vitro drug release profile showed that the increase in urea content led to a slight decrease in Dox release rate. Block copolymer did not have any significant cytotoxicity against HEK293 and HepG2 cells up to 400 mg/L. Importantly, Dox-loaded micelles exerted cytotoxic effect against HepG2 cells.
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http://dx.doi.org/10.1016/j.biomaterials.2010.07.018DOI Listing
November 2010

Self-assembled ferrimagnet--polymer composites for magnetic recording media.

Nano Lett 2010 Aug;10(8):3216-21

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, USA.

A self-assembled magnetic recording medium was created using colloidal ferrimagnetic building blocks. Monodisperse cobalt ferrite nanoparticles (CoFe(2)O(4)) were synthesized using solution-based methods and then stabilized in solution using the amphiphilic diblock copolymer, poly(acrylic acid)-b-poly(styrene) (PAA-PS). The acid groups of the acrylate block bound the polymer to the nanoparticle surface via multivalent interactions, while the styrene block afforded the magnetic nanoparticle--polymer complex solubility in organic solvents. Moreover, the diblock copolymer improved the colloidal stability of the ferrimagnetic CoFe(2)O(4) nanoparticles by reducing the strong interparticle magnetic interactions, which typically caused the ferrimagnetic nanoparticles to irreversibly aggregate. The nanoparticle--polymer complex was spin-coated onto a silicon substrate to afford self-organized thin film arrays, with the interparticle spacing determined by the molecular weight of the diblock copolymer. The thin film composite was also exposed to an external magnetic field while simultaneously heated above the glass transition temperature of poly(styrene) to allow the nanoparticles to physically rotate to align their easy axes with the direction of the magnetic field. In order to demonstrate that this self-assembled ferrimagnet--polymer composite was suitable as a magnetic recording media, read/write cycles were demonstrated using a contact magnetic tester. This work provides a simple route to synthesizing stabilized ferrimagnetic nanocrystals that are suitable for developing magnetic recording media.
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http://dx.doi.org/10.1021/nl1022749DOI Listing
August 2010

Magnetically-responsive self assembled composites.

Chem Soc Rev 2010 Nov 5;39(11):4057-66. Epub 2010 Jul 5.

IBM Almaden Research Center, 650 Harry Road, San Jose, CA 95120, USA.

This tutorial review summarizes the recent advances on the self assembly of magnetic nanoparticles into one-, two-, and three-dimensional architectures using synthetic polymers and biopolymers. The materials have unique stimuli-responsive behavior that emerge in response to internal and external magnetic fields. For example, magnetic fields can be used to elicit a magnetic response from the materials, whether the material rearranges in response to the external field, or provides information regarding the local environment of the nanoparticles. These materials hold great promise for applications ranging from data storage to nanomedicine.
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http://dx.doi.org/10.1039/b812669kDOI Listing
November 2010

Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery.

Biomaterials 2010 Mar 13;31(9):2637-45. Epub 2010 Jan 13.

Center of Innovation and Research in Materials and Polymers (CIRMAP), Laboratory of Polymeric and Composite Materials, University of Mons, Mons, Belgium.

Polymers bearing pendant carbohydrates have a variety of biomedical applications especially in the area of targeted drug delivery. Here we report the synthesis of a family of amphiphilic block glycopolymers containing d glucose, d galactose and d mannose via metal-free organocatalyzed ring-opening polymerization of functional cyclic carbonates generating narrowly dispersed products of controlled molecular weight and end-group fidelity, and their application in drug delivery. These glycopolymers self-assemble into micelles having a high density of sugar molecules in the shell, a size less than 100 nm with narrow size distribution even after drug loading, and little cytotoxicity, which are important for drug delivery. Using galactose-containing micelles as an example, we demonstrate their strong targeting ability towards ASGP-R positive HepG2 liver cancer cells in comparison with ASGP-R negative HEK293 cells although the galactose is attached to the carbonate monomer at 6-position. The enhanced uptake of DOX-loaded galactose-containing micelles by HepG2 cells significantly increases cytotoxicity of DOX as compared to HEK293. This new family of amphiphilic block glycopolymers has great potential as carriers for targeted drug delivery.
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http://dx.doi.org/10.1016/j.biomaterials.2009.12.022DOI Listing
March 2010

Hydrogen-bonding catalysts based on fluorinated alcohol derivatives for living polymerization.

Angew Chem Int Ed Engl 2009 ;48(28):5170-3

Laboratory of Polymeric and Composite Materials, University of Mons-Hainaut, Mons, Belgium.

Recognize this! A hydrogen-bonding motif based on hexafluorinated alcohol derivatives (see picture; O red, F yellow) activates electrophilic substrates. The catalytic activity of the hydrogen-bonded systems was demonstrated for the ring-opening polymerization of a variety of strained heterocycles. Narrowly dispersed polymers with predictable molecular weights were obtained with end-group fidelity.
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http://dx.doi.org/10.1002/anie.200901006DOI Listing
September 2009

A supramolecularly assisted transformation of block-copolymer micelles into nanotubes.

Angew Chem Int Ed Engl 2009 ;48(25):4508-12

IBM Almaden Research Center, 650 Harry Road, San Jose, CA 95120, USA.

Once around the block: Incorporation of a rigid hydrogen-bonding benzamide unit, placed at the interface between two polymer blocks, in poly(ethylene glycol) (PEG)-(thio)urea-poly(L-lactide) (PLLA) block copolymers transforms the morphology of the block copolymers, from spherical micelles, as formed by PEG-PLLA diblock copolymers, into nanotubes in solution.
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http://dx.doi.org/10.1002/anie.200805414DOI Listing
July 2009

Homogeneous catalysis: Catalysts feel the force.

Nat Chem 2009 May 6;1(2):102-3. Epub 2009 Apr 6.

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http://dx.doi.org/10.1038/nchem.189DOI Listing
May 2009

Stimuli-responsive polymers: engineering interactions.

Authors:
Alshakim Nelson

Nat Mater 2008 Jul;7(7):523-5

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http://dx.doi.org/10.1038/nmat2214DOI Listing
July 2008

Multivalent interactions between lectins and supramolecular complexes: Galectin-1 and self-assembled pseudopolyrotaxanes.

Chem Biol 2007 Oct;14(10):1140-51

California NanoSystems Institute, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Supramolecular chemistry has been employed to develop flexible and adaptable multivalent neoglycoconjugates for binding galectin-1 (Gal-1). Gal-1, a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Self-assembled pseudopolyrotaxanes consisting of lactoside-displaying cyclodextrin (LCD) "beads" threaded onto polyviologen "strings" display mobile ligands as a result of cyclodextrin rotation about, and limited translation along, the polymer chain. The pseudopolyrotaxanes rapidly and efficiently precipitate Gal-1 and provide valency-corrected enhancements of up to 30-fold compared to native lactose and 20-fold over free LCD in a T-cell agglutination assay. A supramolecular statistical effect was observed, wherein the efficacy of Gal-1 inhibition correlates with the number of ligands connected to each other solely through mechanical and noncovalent interactions. Such flexible and adaptable self-assembled pseudopolyrotaxanes show promise for the study of multivalent interactions and targeting of therapeutically relevant lectins.
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http://dx.doi.org/10.1016/j.chembiol.2007.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2072908PMC
October 2007