Lowering the modulus of hydrogel particles could enable them to bypass in vivo physical barriers that would otherwise filter particles with similar size but higher modulus. Incorporation of electrolyte moieties into the polymer network of hydrogel particles to increase the swelling ratio is a straightforward and quite efficient way to decrease the modulus. In addition, charged groups in hydrogel particles can also help secure cargoes. However, the distribution of charged groups on the surface of a particle can accelerate the clearance of particles.
Published in JACS, researchers in the DeSimone Group have developed a method to synthesize highly swollen microgels of precise size with near-neutral surface charge while retaining interior charged groups. A strategy was employed to enable a particle to be highly cross-linked with very small mesh size, and subsequently PEGylated to quench the exterior amines only without affecting the internal amines. Acidic degradation of the cross-linker allows for swelling of the particles to microgels with a desired size and deformability. The microgels fabricated demonstrated extended circulation in vivo compared to their counterparts with a charged surface, and could potentially be utilized in in vivo applications including as oxygen carriers or nucleic acid scavengers.
The University of North Carolina at Chapel Hill has long been a leader in innovative thinking that addresses broad challenges. That leadership was on display recently when Joseph DeSimone led a National Research Council committee of top scientists to explore the nation's standing on convergent research, a new approach to help more quickly solve global issues like creating new fuels, securing food supplies and curing disease.
In a report released this month, the NRC committee concluded that better national coordination of convergence is needed to move beyond the current patchwork of efforts across universities and industry and capture the momentum generated in recent years. Both DeSimone and Chancellor Carol L. Folt participated in a September 2013 workshop at the National Academy of Sciences, which led to the committee's work on the report.
Chancellor's Eminent Professor of Chemistry, Joseph DeSimone, has been awarded the 2014 IRI Medal for the commercialization of scientific innovations in areas ranging from plastics manufacturing to nanomedicine which demonstrate significant economic, environmental, and societal impact.
The Industrial Research Institute (IRI) is an organization of over 200 industrial and service companies having a common interest in the effective management of technological innovation. IRI member companies span diverse industries and represent a substantial portion of our nation's gross domestic product. IRI is the only cross-industry organization creating innovation leadership solutions and best practices in innovation management developed through collaborative knowledge creation.
Nanoparticle (NP) drug loading is one of the key defining characteristics of an NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Published in Biomaterials, researchers in the DeSimone Group, characterize the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical.
Particle Replication in Non-wetting Templates, PRINTÂ®, a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel.
Congratulations to Professor Joseph DeSimone and former lab members, Jason Rolland and Ben Maynor, are winners of the 2014 Kathryn C. Hach Award for Entrepreneurial Success from the American Chemical Society!
The winners will be formally presented with the award during a March 2014 National Awards Ceremony at the ACS National Meeting in Dallas. The award recognizes the team's successful efforts to commercialize the PRINT® technology after it was invented in the DeSimone lab in 2004.
A significant limitation in the design of new nanotechnologies for drug delivery is the balance between efficacy, safety, and scalability — the three major hurdles to streamlined approval towards the clinic and, ultimately, adaptation in the pharmaceutical industry. In collaboration with colleagues at MIT, researchers in the DeSimone Group, published in Advanced Materials, combine PRINT® technology with spray-assisted, layer-by-layer deposition to generate uniform and functional nanotechnologies with precise control over composition, size, shape, and surface functionality.
This new methodology demonstrates a modular and tunable approach towards design of built-to-order nanoparticle systems. The ability to spray coat PRINT® particles promises to achieve technologies capable of targeted interactions with cancer cells for applications in drug delivery.
In an article published in Nano Letters, the DeSimone Group, in collaboration with the departments of Cell and Developmental Biology, Pharmacology, Biochemistry and Biophysics, the Carolina Center of Cancer Nanotechnology Excellence, the Institute for Advanced Materials, Howard Hughes Medical Institute, the Institute for Nanomedicine, Lineberger Comprehensive Cancer Center, Department of Chemical and Biomolecular Engineering at North Carolina State University, and the Sloan-Kettering Institute for Cancer Research, varied PEGylation density on the surface of hydrogel PRINT nanoparticles and systematically observed the effects on protein adsorption, macrophage uptake, and circulation time.
Interestingly, the density of PEGylation necessary to promote a long-circulating particle was dramatically less than what has been previously reported. Overall, the methodology used provides a rapid screening technique to predict particle behavior in vivo and the results deliver further insight into what PEG density is necessary to facilitate long-circulation.
The American Chemical Society has named Carolina Chemistry professors Royce Murray and Joseph DeSimone as ACS Fellows. The new class of ninety-six fellows will be honored at the society's fall national meeting in Philadelphia this August. The ceremony will be hosted by ACS Immediate Past-President Nancy B. Jackson.
"ACS is especially proud to honor these chemists, who have given so much to the community and the profession," said Jackson in announcing the 2012 class of ACS Fellows. "They are leaders whose work is having a lasting beneficial impact, not just on science but also on the ACS community." Their contributions include outstanding and creative scientific research, superior achievements in the teaching and learning of chemistry, managerial excellence, and volunteer service through meetings and communication with the public, she noted.
The fellows program began in 2009 as a way to recognize and honor ACS members for outstanding achievements in and contributions to science, the profession, and ACS.
Published in JACS, researchers in the DeSimone Group describe how asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics were synthesized and incorporated within 200 nm Ã— 200 nm particles. ABS prodrugs of gemcitabine were selected as model compounds because of the difficulty to encapsulate a water-soluble drug within a hydrogel.
The resulting drug delivery systems were degraded under acidic conditions and were found to release only the parent or active drug. Furthermore, changing the steric bulk of the alkyl substituents on the silicon atom could regulate the rate of drug release and, therefore, the intracellular toxicity of the gemcitabine-loaded particles. This yielded a family of novel nanoparticles that could be tuned to release drug over the course of hours, days, or months.
Matthew Detter, a senior chemistry major, studying in the DeSimone Group, has been selected as a recipient of The Venable Medal.
The Venable Medal was established in 1955 by Rho Chapter of Alpha Chi Sigma and is presented annually by members of that professional chemistry fraternity to the two most outstanding seniors majoring in chemistry. The selection is based on scholastic and academic work within the chemistry program, and outstanding academic work, character, and outstanding contributions to the University community and to chemistry. The award bears the name of Francis Preston Venable, chemistry professor from 1880 to 1930 and president of the University from 1900 to 1914.
In Engines of Innovation, UNC Chapel Hill Chancellor Holden Thorp and Buck Goldstein, the University's "entrepreneur in residence," make the case for the pivotal role of research universities as agents of societal change. They argue that universities must use their vast intellectual and financial resources to confront global challenges such as climate change, extreme poverty, childhood diseases, and an impending worldwide shortage of clean water.
David Rohde, a a columnist for Reuters, two-time winner of the Pulitzer Prize, and a former reporter for The New York Times, discusses Engines of Innovation in a column in the journal Atlantic. Among examples of successful entrepreneuship started at universities, the article cites UNC chemistry professor Joe DeSimone as a best-case scenario. Last year, a private company DeSimone founded with the help of his university research received a $10 million investment from the Bill and Melinda Gates Foundation. The funding will help the company, Liquidia Technologies, develop new vaccines for malaria and other diseases.
Chancellor's Eminent Professor of Chemistry Joseph DeSimone has been awarded the 2012 Walston Chubb Award for Innovation. This recognition is awarded by the the Scientific Research Society Sigma Xi to recognize research into new areas of potential scientific importance, novel approaches to a long-standing problem in science or engineering, or research that may create a new methodology of importance to science or engineering.
In March of 2011, the Bill & Melinda Gates Foundation made a $10 million program-related investment in UNC Chemistry spinoff company Liquidia Technologies. This was the Foundation's first-ever equity investment in a biotech company. Liquidia was founded in 2004 by Professor Joseph DeSimone and colleagues based on the Particle Replication In Non-wetting Templates, PRINT, technology invented in DeSimone's lab. Using PRINT, Liquidia focuses on developing highly precise particle-based vaccines and therapeutics for the prevention and treatment of human disease.
Featured in the July issue of Nature Biotechnology, this investment is a unique precedent for partnerships among philanthropies, for-profit investors, and biotech companies with shared interests in addressing large-scale, global health issues. "In particular, the fact that it does not exclude the possibility of also receiving grants is excellent," comments DeSimone. This leaves room for potential future funding for projects that Liquidia may not be able to pursue otherwise, such as developing cost-effective, next-generation vaccines for preventable diseases in developing countries. This potential would not exist without the strong, foundational research conducted in our academic labs at UNC. "We are the catalyst," says DeSimone enthusiastically.
Congratulations to Dr. Jin Wang, who will join the Baylor College of Medicine (BCM) faculty this coming fall as a Cancer Prevention Research Institute of Texas (CPRIT) Scholar in Cancer Research. Wang is the latest recipient of a $2 million CPRIT award for new faculty, which recognizes investigators with the ability to make outstanding contributions to the field of cancer research, promote inquiry into new areas, foster collaboration, and stimulate growth in the field. A $1 million match from Baylor brings the total to $3 million.
Leaving his postdoc position with the DeSimone Group, Wang will take on the roles of assistant professor in the Department of Pharmacology at BCM, member of the NCI-designated Dan L. Duncan Cancer Center, and adjunct faculty member in the Department of Bioengineering at Rice University. Wang will build on his research achievements at UNC, focusing on applications of nanotechnology in biomedicine, including targeted drug delivery for cancer therapies. "The postdoc training in Dr. DeSimone's group has broadened my horizons significantly, and in ways I could have never imagined as a graduate student in organic chemistry," Wang said. "Dr. DeSimone not only mentors us toward achievements in science, but also teaches us how to be entrepreneurial and apply our knowledge to make an impact on other people's lives."
Developed in the DeSimone Group, the PRINTâ„¢ particle technology has been chosen by PATH Malaria Vaccine Initiative (MVI) to design a next generation of malaria vaccines. PRINTâ„¢ technology offers unprecedented control of particle size, shape and chemistry in a highly consistent and scalable manufacturing process, and will be used to deliver a protein in combination with immune stimulating molecules. The vaccine candidate will target the preâ€erythrocytic stage of the parasite and is designed to enhance both the frequency and longevity of the humoral and cellular immune response to Plasmodium falciparum.
MVI is responsible for the malaria vaccine development program at PATH, an international nonprofit organization working to improve global health. Established in 1999, MVI works to accelerate the development of malaria vaccines and to ensure their availability and accessibility in the developing world.
A collaborative effort published in Nano Letters by the DeSimone Group, reports the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT (Particle Replication in Nonwetting Templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%.
The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere.
A collaborative effort under the direction of Chancellor's Eminent Professor Joseph DeSimone, published in JACS, featured in C&E News, and also in Nature Chemistry discusses how responsive polymeric biomaterials can be triggered to degrade using localized environments found in vivo. A limited number of biomaterials provide precise control over the rate of degradation and the release rate of entrapped cargo and yield a material that is intrinsically nontoxic. In their work, the researchers designed nontoxic acid-sensitive biomaterials based on silyl ether chemistry. A host of silyl ether cross-linkers were synthesized and molded into relevant medical devices, including Trojan horse particles, sutures, and stents.
The resulting devices were engineered to degrade under acidic conditions known to exist in tumor tissue, inflammatory tissue, and diseased cells. The implementation of silyl ether chemistry gave precise control over the rate of degradation and afforded devices that could degrade over the course of hours, days, weeks, or months, depending upon the steric bulk around the silicon atom. These novel materials could be useful for numerous biomedical applications, including drug delivery, tissue repair, and general surgery.
In a collaborative effort between researchers at the University of Chicago, Lawrence Berkeley National Laboratories, and Liquidia Technologies, the DeSimone Group, as published in the Journal of Rheology, has investigated confined shear thickening suspensions for which the sample thickness is comparable to the particle dimensions. Rheometry measurements are presented for densely packed suspensions of spheres and rods with aspect ratios 6 and 9. By varying the suspension thickness in the direction of the shear gradient at constant shear rate, the investigators found pronounced oscillations in the stress. These oscillations become stronger as the gap size is decreased, and the stress is minimized when the sample thickness becomes commensurate with an integer number of particle layers.
Despite this confinement-induced effect, viscosity curves show shear thickening that retains bulk behavior down to samples as thin as two particle diameters for spheres, below which the suspension is jammed. Rods exhibit similar behavior commensurate with the particle width, but they show additional effects when the thickness is reduced below about a particle length as they are forced to align; the stress increases for decreasing gap size at fixed-shear rate while the shear thickening regime gradually transitions to a Newtonian scaling regime. This weakening of shear thickening as an ordered configuration is approached contrasts with the strengthening of shear thickening when the packing fraction is increased in the disordered bulk limit, despite the fact that both types of confinement eventually lead to jamming.
The search for a method to fabricate nonspherical colloidal particles from a variety of materials is of growing interest. As the commercialization of nanotechnology continues to expand, the ability to translate particle-fabrication methods from a laboratory to an industrial scale is of increasing significance. In an article featured on the cover of Langmuir, members of the DeSimone Group examine several of the most readily scalable top-down methods for the fabrication of such shape-specific particles and compare their capabilities with respect to particle composition, size, shape, and complexity as well as the scalability of the method.
The group offers an extensive examination of particle replication in nonwetting templates, PRINT©, with regard to the versatility and scalability of this technique. They also detail the specific methods used in PRINT© particle fabrication, including harvesting, purification, and surface-modification techniques, with an examination of both past and current methods.
Members of the DeSimone Group have developed a novel composite film fabrication process that utilizes the soft lithographic approach, Particle Replication in Nonwetting Templates, PRINT®. This process was found to be a very viable approach to the fabrication of well-structured, multifunctional polymer composite thin films. As published in Chemistry of Materials, particle aggregation was completely eliminated as discretely molded particles with specific shape, size and composition were maintained in well-defined arrays determined by the silicon master template.
Both all-organic and polymer-ceramic composites have been generated using this technique with particle inclusions ranging in size from 200 nm to 20 µm. The composition of the composite was well-controlled with both cross-linked and thermoplastic polymeric continuous phases, as well as particle compositions ranging from cross-linked polymeric resins to the inorganic oxide, barium titanate.
The Rochester Section of the American Chemical Society has elected to award Chancellor's Eminent Professor of Chemistry Joseph DeSimone the 2011 Harrison Howe Award. This award was inaugurated in 1946 to honor one of the founders of the Rochester ACS Section. In addition to his role as a leader in that capacity, Harrison Howe was also the founding editor of Chemical and Engineering News and a fervent champion of industrial research and development. It was his belief that chemistry and the pursuit of chemical knowledge contribute to the betterment of society.
The Harrison Howe Award will be granted to an individual without regard to nationality for outstanding contributions to research in chemistry defined in its broadest sense. A distinguishing feature of the award is that many of the recipients have been recognized in the early stages of their careers and with potential for further outstanding achievement. As of 2009, 40% of Harrison Howe Award winners have eventually gone on to receive the Nobel Prize in Chemistry.
The National Science Foundation, NSF, is celebrating the achievements of five leading Science and Technology Centers, STC, that have been conducting world-class research and education programs since 2000 in varied disciplines with NSF funding. Each STC received a total of $38 million under its own cooperative agreement with NSF that concluded in 2010. Among the five centers recognized is the Science and Technology Center for Environmentally Responsible Solvents and Processes under the direction of UNC Chemistry faculty member Joseph DeSimone.
This STC is the world's leading center for enabling and discovering sustainable processes and products that use CO2-related technology. In addition, by fostering innovation and applying its discoveries to the development of sustainable energy alternatives, medical diagnostics and therapeutics via targeted delivery, its achievements have had broad societal benefits, including the catalytic role of its launch of eight start-up companies. Additionally, they have successfully engaged the public in science through various forums, including the NBTC Nanobiotechnology Center's traveling exhibit, It's a Nanoworld.
Researchers in the DeSimone Group, using Particle Replication In Nonwetting Templates (PRINT ®) technology, have fabricated multiphasic and regio-specifically functionalized shape-controlled particles that include end-labeled particles via post-functionalization; biphasic Janus particles that integrate two compositionally different chemistries into a single particle; and more complex multiphasic shape-specific particles.
Controlling the anisotropic distribution of matter within a particle creates an extra parameter in the colloidal particle design, providing opportunities to generate advanced particles with versatile and tunable compositions, properties, and thus functionalities. Owing to their robust characteristics, these multiphasic and regio-specifically functionalized PRINT particles should be promising platforms for applications in life science and materials science.
In collaboration with researchers from UNC-CH Physics and Astronomy Department, investigators in the Samulski Group, and the DeSimone Group report organic solar cells with a photonic crystal nanostructure embossed in the photoactive bulk heterojunction layer, a topography that exhibits a 3-fold enhancement of the absorption in specific regions of the solar spectrum in part through multiple excitation resonances. The photonic crystal geometry is fabricated using a materials-agnostic process called PRINT wherein highly ordered arrays of nanoscale features are readily made in a single processing step over wide areas (4 cm2) that is scalable.
The research show efficiency improvements of 70% that result not only from greater absorption, but also from electrical enhancements. The methodology is generally applicable to organic solar cells and the experimental findings reported in the manuscript corroborate theoretical expectations.
Researchers in the DeSimone Group describe how Amphiphilic networks of perfluoropolyethers (PFPE) and poly(ethylene glycol) (PEG) have been achieved to yield optically transparent, mechanically robust films over a wide range of compositions. Telechelic diols of these oligomers were transformed to a photocurable dimethacryloxy form (DMA) and free radically cured at various composition weight ratios to yield free-standing films. Clear and colorless amphiphilic networks could be achieved when low molar mass versions of both the PFPE-DMA (1 kg/mol) and the PEG-DMA (550 g/mol) were used.
The bulk morphologies of the samples were extensively characterized by a variety of techniques including ultravioletâˆ’visible spectroscopy, differential scanning calorimetry, dynamic mechanic thermal analysis, small-angle X-ray scattering, atomic force microscopy, X-ray photoelectron spectroscopy, and optical microscopy, which strongly suggest that nanoscopic to macroscopic phase-separated materials could be achieved. By incorporating a threshold amount of PFPEs into PEG-based hydrogel networks, water swelling could be significantly reduced, which may offer a new strategy for a number of medical device applications. Along these lines, strong inhibition of nonspecific protein adsorption could be achieved with these amphiphilic network materials compared with an oligo(ethylene glycol)-based self-assembled monolayer coated surface.
The synthesis of prodrugs is a common approach to overcome drug delivery issues, including poor aqueous solubility or permeability, and to provide site-specific release. Nanotechnology can be a powerful tool to improve drug delivery, but does so by altering the biodistribution of the encapsulated small molecule. In a report published in NanoLetters, researchers in the DeSimone Group, in collaboration with a number of Centers, Institutes, and Departments here at UNC, combined the merits of both approaches to improve the pharmacokinetics and toxicity of the chemotherapeutic docetaxel by passively targeting an encapsulated docetaxel prodrug to solid tumors, where it could selectively release and convert to active docetaxel.
The Group used PRINT technology, Particle Replication in Nonwetting Templates, to prepare nanoparticles to passively target solid tumors in an A549 subcutaneous xenograft model. An acid labile prodrug was delivered to minimize systemic free docetaxel concentrations and improve tolerability without compromising efficacy.
In studying a material that prevents marine life from sticking to the bottom of ships, researchers led by Carolina Chemistry's Joseph DeSimone, have identified a surprising replacement for the only inherently flammable component of today's lithium-ion batteries: the electrolyte.
The work, published in the Proceedings of the National Academy of Sciences, not only paves the way for developing a new generation lithium-ion battery that does not spontaneously combust at high temperatures, but also has the potential to —after recent lithium battery fires in Boeing 787 Dreamliners and Tesla Model S vehicles— renew consumer confidence in a technology that has attracted significant concern.
Joseph DeSimone, Chancellor's Eminent Professor of Chemistry at the University of North Carolina at Chapel Hill and the William R. Kenan Jr. Professor of Chemical Engineering at NC State University, has been named a fellow of the National Academy of Inventors, NAI. The NAI honors academic inventors with a prolific spirit of innovation in creating inventions that have made an impact on quality of life, economic development and the welfare of society.
DeSimone will be inducted by the deputy U.S. commissioner for patents, Andy Faile, during the third annual Conference of the National Academy of Inventors on March 7, 2104, at the U.S. Patent and Trademark Office in Alexandria, VA.
Published in Molecular Pharmaceutics, scientists in the DeSimone Group report on the development of a nonviral lipid-complexed PRINT, Particle Replication in Nonwetting Templates, protein particle system, LPP particle, for RNA replicon delivery with a view toward RNA replicon-based vaccination. Cylindrical bovine serum albumin, BSA, particles with a diameter, d, of 1 Î¼m, height, h, 1 Î¼m, loaded with RNA replicon and stabilized with a fully reversible disulfide cross-linker were fabricated using PRINT technology.
Highly efficient delivery of the particles to Vero cells was achieved by complexing particles with a mixture of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipids. Our data suggest that (1) this lipid-complexed protein particle is a promising system for delivery of RNA replicon-based vaccines and (2) it is necessary to use a degradable cross-linker for successful delivery of RNA replicon via protein-based particles.
A new $4.47 million project in the DeSimone Group at Carolina Chemistry, funded by the Defense Threat Reduction Agency, will help lay the groundwork for developing potentially better ways to deliver antidotes against exposure to chemical weapons. The work could ultimately help both civilian and military populations through the design of precisely engineered particles and microneedle patches that are loaded with a nerve gas antidote that can be easily administered in the event of an attack.
Researchers in the DeSimone Group will use the PRINT® technology, also known as Particle Replication In Non-wetting Templates, to design and optimize the size, shape and composition of particles and microscopic needles that can carry life-saving antidotes to chemical nerve gas. If successful, the application of this technology could make it easier to deliver drugs faster to counteract severe reactions to chemical agents.
Sigma Xi, the Scientific Research Society, selected Chancellor's Eminent Professor of Chemistry Joseph DeSimone to receive the 2012 Walston Chubb Award for Innovation. The Chubb Award is designed to honor and promote creativity among scientists and engineers.
Professor DeSimone was selected for successfully adapting lithographic techniques from the computer industry to create a new technology for fabricating precisely defined micro- and nanoparticles for applications including new vaccines and therapeutics.
In an interview with Cathy Clabby, American Scientist Contributing Editor, DeSimone describes his journey as an innovative and entrepreneurial scientist, the power of cross-disciplinary research, the process of moving innovation from the laboratory to society, the value of diversity in a research team, his exciting collaboration with the Gates Foundation, and the challenges to future innovation.
In collaboration with UNC groups at the Eshelman School of Pharmacy, the Carolina Center of Cancer Nanotechnology Excellence, the Institute for Advanced Materials, the Institute for Nanomedicine, Lineberger Comprehensive Cancer Center, the Department of Chemical and Biomolecular Engineering at North Carolina State University, and the Sloan-Kettering Institute for Cancer Research, the DeSimone Group, as published in Biomacromolecules, have synthesized extremely deformable red blood cell-like microgel particles and loaded them with bovine hemoglobin, Hb, to potentiate oxygen transport. With similar shape and size as red blood cells, the particles were fabricated using the PRINT® technique developed in DeSimone's lab.
Hemoglobin-loaded particles with moderate loading ratios demonstrated excellent deformability in microfluidic devices, easily deforming to pass through restricted pores half as wide as the diameter of the particles. The suspension of concentrated particles with a Hb concentration of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles remained intact even after being sheared at a constant high rate, 1000 1/s, for 10 min. Armed with the ability to control size, shape, deformability, and loading of Hb into red blood cell mimics, the researchers believe that these Hb-loaded particles provide a promising start toward the next generation of blood substitutes.
Published in Langmuir, researchers from the DeSimone Group describe the fabrication of filamentous hydrogel nanoparticles using a unique soft lithography based particle molding process referred to as PRINT; Particle Replication in Nonwetting Templates. The nanoparticles possess a constant width of 80 nm, and the group members varied their lengths ranging from 180 to 5000 nm. In addition to varying the aspect ratio of the particles, the deformability of the particles was tuned by varying the cross-link density within the particle matrix.
Size characteristics such as hydrodynamic diameter and persistence length of the particles were analyzed using dynamic light scattering and electron microscopy techniques, respectively, while particle deformability was assessed by atomic force microscopy. Additionally, the ability of the particles to pass through membranes containing 0.2 Î¼m pores was assessed by means of a simple filtration technique, and particle recovery was determined using fluorescence spectroscopy.
A critical need exists for effective delivery of RNA interference (RNAi) therapeutics to target tissues and cells. Self-assembled lipid- and polymer-based systems have been most extensively explored for transfection with small interfering RNA (siRNA) in liver and cancer therapies. Safety and compatibility of materials implemented in delivery systems must be ensured to maximize therapeutic indices. In a collaborative work published in JACS, scientists in the DeSimone Group explore hydrogel nanoparticles of defined dimensions and compositions, prepared via a particle molding process that is a unique off-shoot of soft lithography known as particle replication in nonwetting templates (PRINT), as delivery vectors.
Initially, siRNA was encapsulated in particles through electrostatic association and physical entrapment. Dose-dependent gene silencing was elicited by PEGylated hydrogels at low siRNA doses without cytotoxicity. To prevent disassociation of cargo from particles after systemic administration or during postfabrication processing for surface functionalization, a polymerizable siRNA pro-drug conjugate with a degradable, disulfide linkage was prepared. Triggered release of siRNA from the pro-drug hydrogels was observed under a reducing environment while cargo retention and integrity were maintained under physiological conditions.
Gene silencing efficiency and cytocompatibility were optimized by screening the amine content of the particles. When appropriate control siRNA cargos were loaded into hydrogels, gene knockdown was only encountered for hydrogels containing releasable, target-specific siRNAs, accompanied by minimal cell death. Further investigation into shape, size, and surface decoration of siRNA-conjugated hydrogels should enable efficacious targeted in vivo RNAi therapies.
The 2012 edition of "Profiles in Team Science," published by the National Science Foundation, explores outcomes of team science that may not easily be covered within the constraints of the news media. The issue aims to bridge the news gap causing many members of the general public to be unaware of, or make connections between, research centers and the results they produce.
One of the articles highlights the work of the Center for Environmentally Responsible Solvents and Processes, CERSP, directed by Chancellor's Eminent Professor Joseph DeSimone. The center's initial goal was to establish the science enabling the replacement of aqueous and organic solvents in a large number of key processes in the manufacturing sector with liquid and supercritical CO2. Demonstrating the power of team science, CERSP's work led serendipitously to the PRINT technology. "It just shows the unbounded opportunities that happen when you get a bunch of good people together from different disciplines that are open-minded," says Professor DeSimone.
Chancellor's Eminent Professor of Chemistry, Joseph DeSimone was invited to talk at the 2011 TedMed gathering. His presentation focused on how an amazing new printing technique, borrowed from the micro electronics industry, enhances biomimicry for drugs that target diseased cells and bacteria, not healthy tissue.
TEDMED is a community of people who are passionate about a better future for health and medicine. Once a year, TEDMED holds a "grand gathering" where leaders from all sectors of society come together for three and a half days. They explore the promise of technology and the potential of human achievement. This unique event combines dazzling celebration, high-powered learning and unforgettable theater.
Chancellor's Eminent Professor of Chemistry, Joseph DeSimone, will collaborate with scientists at Beth Israel Deaconess Medical Center/Harvard and Johns Hopkins University to develop a nanoparticle vaccine for prostate cancer. The Prostate Cancer Foundation awarded the team one of their Challenge Awards, designed to support cross-disciplinary groups of prostate cancer investigators who are focused on highly innovative research with potential for near-term patient benefit.
According to DeSimone, "UNC researchers, in partnership with scientists at Carolina spin-off biotechnology company Liquidia, will focus on the particle fabrication and optimization aspects of the project, which will involve the development of particles, analytical evaluation, and initial testing." The UNC team will then work with collaborators at Harvard and Johns Hopkins to test the particles in validated models.
The Prostate Cancer Foundation is the world's largest philanthropic source of support for accelerating the most promising research for better treatments and cures for prostate cancer.
An article stemming from a collaboration between the Samulski and DeSimone groups, published in the journal Soft Matter, is one of the top ten most read articles of the online version of the publication. The researchers report a replication route to non-planar, three-dimensional microlens arrays with an antireflective surface nanopattern, using the surface topography of the Attacus atlas moth's compound eye.
Soft lithographic techniques gave topographically faithful moulds that, in turn, were used to reproducibly and repeatedly replicate the original eye surface with nanoscale fidelity. In addition to antireflection, the resulting poly(urethane) replica with its "moth-eye" nanopattern also exhibited increased hydrophobicity. The materials flexibility of the perfluoropolyether mould fabricated via replica moulding also enables the embossing of antireflective nanopatterns in, for example, photoactive materials for organic solar cells.
The Triangle-based UNC Chemistry spinoff company Liquidia, which is at the forefront of efforts to use nanotechnology to tackle diseases, has received a $10 million investment from the Bill & Melinda Gates Foundation.
Liquidia Technologies, which was founded on the discoveries of Carolina Chemistry professor Joseph DeSimone, will use the foundation's equity investment to support the development and commercialization of safer and more effective vaccines and therapeutics.Liquidia uses PRINTâ„¢ technology, a technique invented in DeSimone's UNC chemistry lab, to manufacture precisely engineered nano- and microparticles with control over size, shape and chemistry. It could advance the development of vaccines to prevent diseases, such as malaria, that mainly affect people in the developing world. "This technology has the potential to help countless people, maybe save millions of lives," DeSimone said. "To have the Gates Foundation back our work is a heartening vindication of UNC's effort to become a world leader in launching university-born ideas for the good of society."
A team of scientists under the direction of Joseph DeSimone, has created particles that closely mirror some of the key properties of red blood cells, potentially helping pave the way for the development of synthetic blood. It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. The investigators synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo.
Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results, published in PNAS, demonstrate a critical design parameter for hydrogel microparticles.
Researchers in the DeSimone Group demonstrate a facile way of cross-linking hydrophobic perfluoropolyethers, PFPEs, with a series of hydrophilic poly(ethylene glycol)s, PEGs, to prepare a range of amphiphilic networks for use as fouling-release coatings.
As described in Macromolecules, the PFPE matrix of the networks endows the coating with a low surface energy while the PEG is added to weaken fouling adhesion. It is therefore envisioned that the coating surfaces of these optically transparent and mechanically robust films will display hydrophobicity leading to nonfouling and fouling release characteristics.
Chancellor's Eminent Professor Joseph DeSimone has been selected to receive the 2010 American Association for the Advancement of Science's Mentor Award. The award honors DeSimone's dedication to advancing diversity in the chemistry PhD workforce.
Established by the AAAS Board of Directors in 1996, this award recognizes AAAS members who have mentored significant numbers of students from underrepresented groups towards a PhD in the sciences, or who have changed the climate of a department, college or institution, to significantly increase the diversity of students pursuing and completing doctoral studies in the sciences.
The National Cancer Institute has awarded a five-year, $13.6 million grant to the University of North Carolina at Chapel Hill's Carolina Center of Cancer Nanotechnology Excellence, based at the UNC Lineberger Comprehensive Cancer Center, for research to improve the diagnosis and treatment of cancer through applying/using advances in nanotechnology. The grant will support the continued work of the center launched in 2005 as part of NCI's Alliance for Nanotechnology in Cancer.
The C-CCNE, one of eight original centers in the national program, is one of nine that are funded in the new phase. Professor Joseph DeSimone, who will co-lead the C-CCNE research team said, "Our efforts in nanomedicine show tremendous promise for improving the ways we detect and treat lung, brain, and breast cancer. We have refined our ability to make nanoparticles with unprecedented control and precision, and continued work in this area will reveal better approaches to targeting cancer cells with potent therapies while leaving healthy cells intact."
Transferrin receptor has long been a therapeutic target due to its overexpression in many malignant tissues. In a collaborative study published in JACS, the DeSimone Group, describes how PRINT® nanoparticles were conjugated with TfR ligands for targeted drug delivery. Cylindrical poly(ethylene glycol)-based PRINT nanoparticles labeled with transferrin receptor antibody, NP-OKT9, or human transferrin, NP-hTf, showed highly specific TfR-mediated uptake by all human tumor cell lines tested, relative to negative controls, IgG1 for OKT9 or bovine transferrin, bTf for hTf. The targeting efficiency was dependent on particle concentration, ligand density, dosing time, and cell surface receptor expression level.
Interestingly, NP-OKT9 or NP-hTf showed little cytotoxicity on all solid tumor cell lines tested but were very toxic to Ramos B-cell lymphoma, whereas free OKT9 or hTf was not toxic. There was a strong correlation between TfR ligand density on the particle surface and cell viability and particle uptake. NP-OKT9 and NP-hTf were internalized into acidic intracellular compartments but were not localized in EEA1-enriched early endosomes or lysosomes. Elevated caspase 3/7 activity indicates activation of apoptosis pathways upon particle treatment. Supplementation of iron suppressed the toxicity of NP-OKT9 but not NP-hTf, suggesting different mechanisms by which NP-hTf and NP-OKT9 exerts cytotoxicity on Ramos cells.
On the basis of such an observation, the DeSimone Group discusses the complex role of multivalency in nanoparticles. In addition, the group's data clearly reveal that one must be careful in making claims of "lack of toxicity" when a targeting molecule is used on nanoparticles and also raise concerns for unanticipated off-target effects when one is designing targeted chemotherapy nanodelivery agents.
Joseph DeSimone, PhD, Chancellor's Eminent Professor of Chemistry at Carolina, William R. Kenan Jr. Distinguished Professor of Chemical Engineering at NCSU, a member of UNC Lineberger Comprehensive Cancer Center, and founder of the nanobiotechnology firm Liquidia Technologies, has been appointed as an adjunct member at New York's Memorial Sloan-Kettering Cancer Center's Cancer Nanocenter. The appointment is part of a strategic alliance aimed at building Sloan-Kettering's capabilities in nanomedicine and broadening the geographic base of DeSimone's pioneering work based in North Carolina.
"Our work is advancing the field of vaccines, which is a traditional strength of Memorial Sloan-Kettering. Additionally, the geographical location of Memorial Sloan Kettering in New York and its large, diverse patient base will both complement and enhance the reach of the work being done at UNC and N.C. State in medical imaging, radiation therapy, cancer vaccines and pharmaceutical therapies as well as in the new field of interventional oncology, where we are working to deliver therapies directly to the area of the body affected by cancer," said DeSimone.
In a collaborative effort between the DeSimone Group, the Templeton Group, and the Department of Chemical and Biomolecular Engineering, North Carolina State University at Raleigh, published in Langmuir, ordered, two-dimensional cadmium selenide (CdSe) arrays have been fabricated on indium-doped tin oxide (ITO) electrodes using the pattern replication in nonwetting templates, PRINT® process. CdSe quantum dots (QDs) with an average diameter of 2.7 nm and a pyridine surface ligand were used for patterning.
The PRINT® technique utilizes a perfluoropolyether (PFPE) elastomeric mold that is tolerant of most organic solvents, thus allowing solutions of CdSe QDs in 4-picoline to be used for patterning without significant deformation of the mold. Nanometer-scale diffraction gratings have been successfully replicated with CdSe QDs.
Suspensions are of wide interest and form the basis for many smart fluids. For most suspensions, the viscosity decreases with increasing shear rate; that is, they shear thin. Few are reported to do the opposite, that is, shear thicken, despite the longstanding expectation that shear thickening is a generic type of suspension behavior. As published in Nature Materials, researchers in the DeSimone Group with collaborators at the University of Chicago and Liquidia Technologies have resolved this apparent contradiction.
The team has demonstrated that shear thickening can be masked by a yield stress and can be recovered when the yield stress is decreased below a threshold. They have shown the generality of this argument and have quantified the threshold in rheology experiments where they controlled yield stresses arising from a variety of sources, including attractions from particle surface interactions, induced dipoles from applied electric and magnetic fields, as well as confinement of hard particles at high packing fractions. These findings open up possibilities for the design of smart suspensions that combine shear thickening with electro- or magnetorheological response.
Joseph DeSimone, the Chancellor's Eminent Professor of Chemistry at UNC Chapel Hill and the co-founder of Liquidia Technologies was recently featured in the Herald Sun describing a prototype of a new device that he and the DeSimone Group at UNC are developing. The device would allow for minimally invasive electric field-assisted, local delivery of small molecule chemotherapies, biologicals, and chemotherapy-loaded nanoparticles for the treatment of pancreatic adenocarcinoma
The device, pictured above, could be capable of efficient and uniform delivery by overcoming the various biological barriers common to pancreatic tumors, including the up-hill gradients in flow and pressure. This technology could potentially offer an entirely new modality for the treatment of pancreatic adenocarcinoma under the emerging field of interventional oncology. The inspiration for the design of the prototype device was drawn from innovations in the fields of medical devices, nanomedicine and oncology.
As published in The Journal of Supercritic Fluids, researchers in the DeSimone Group review the environmentally friendly synthesis of fluorinated polymers in supercritical carbon dioxide (scCO2). Historically, many high-performance fluorinated materials are commercially synthesized in aqueous media using fluorinated surfactants or in non-aqueous conditions using fluorinated solvents. The DeSimone Group group has pioneered both the homogeneous and heterogeneous polymerization of fluorinated monomers in scCO2. The article includes discussions on the synthesis of main-chain and side-chain fluoropolymers conducted via a chain-growth or continuous process.
In general, many commercial fluoropolymers have been successfully prepared in scCO2 or CO2-based media. These fluoropolymers have superior or comparable properties to the commercial products manufactured in conventional media such as CFCs or water. Carbon Dioxide is becoming an environmentally sensible and industrially viable replacement in many cases. Moreover, its unique properties as a polymerization medium are enabling the development of many new fluorinated polymers or composite materials which are otherwise difficult or impossible to realize. The study in this area is getting more exciting since such laboratory successes may be commercialized more quickly without the competition from existing products or existing conventional equipment and processes.
The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. A team of researchers led by Joseph DeSimone, Ph.D., Chancellor's Eminent Professor of Chemistry at UNC-CH, report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. The group employs a top-down particle fabrication technique called PRINT®, Particle Replication in Non-wetting Templates, that is able to generate uniform populations of organic micro- and nanoparticles with complete control of size, shape, and surface chemistry.
Evidence of particle internalization was obtained by using conventional biological techniques and transmission electron microscopy. These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 µm by using several different mechanisms of endocytosis. Moreover, it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates, reminiscent of the advantage that many rod-like bacteria have for internalization in nonphagocytic cells.