1993 — 2001 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Chemistry of Luminescent Porous Silicon @ University of California-San Diego
The goal of this work is to understand the origin of luminescence in porous silicon, and to explore the relationship between luminescence and surface chemistry of this material. The first goal will be achieved by testing the three current hypotheses explaining photoluminescence in porous silicon. The second goal will be achieved by observing the changes that occur in emission intensity, wavelength, and lifetimes on exposure of the materials to various chemical reagents such as Lewis acids or bases, electron, hole, or energy transfer agents, and polar or polarizable species. The mechanism of luminescence quenching of porous silicon by gas phase species will be studied. The silicon surface chemistry will by developed by tuning the quenching response for specific adsorbates. The unique ability of porous silicon to change its fluorescence color and intensity in the presence of chemical adsorbates opens up a range of possible application for gas, liquid, and biological sensors. In addition, an understanding of the fundamental photophysics of porous silicon under these conditions may lead to the development of full-color flat panel electroluminescence displays. these potential development can build on well- established silicon processing technology. The key contribution of the proposed work is that it will define the chemical and photochemical reactivity patterns of luminescent porous silicon, providing the design rules for the development of such applications.
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0.915 |
1993 — 1998 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nsf Young Investigator @ University of California-San Diego
9357415 Sailor This NSF Young Investigator award deals with research and teaching in areas that include the chemistry of luminescent porous silicon, and the role of chemical adsorbates and surface chemical reactions. The potential of these materials for uses such as chemical and bio- sensors, and detector and display applications will be evaluated. ***
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0.915 |
1997 — 1999 |
Sailor, Michael J |
S06Activity Code Description: To strengthen the biomedical research and research training capability of ethnic minority institutions, and thus establish a more favorable milieu for increasing the involvement of minority faculty and students in biomedical research. |
Chemically Turnable Porous Si Sensors For in Situ Monitoring of Toxins @ University of California San Diego
The color and intensity of the light given off from photoluminescent porous silicon can be modified by chemical adsorbates. For example, when porous silicon is exposed to vapors of the carcinogen benzene, its luminescence intensity drops by more than 50%. The effect is reversible, so when the chemical evaporates off, the original intensity of the luminescence is recovered. A variety of polyaromatic hydrocarbons affect porous silicon in a similar fashion. This property demonstrates the feasibility of using porous Si in gas or liquid sensors. The students involved in the proposed project will quantify the response of porous silicon toward polyaromatic hydrocarbons, carbon monoxide, nitric oxide, carbon dioxide, and heavy metals, in order to define the potential for this material to act as a sensor for these biologically relevant chemicals.
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1 |
1999 — 2003 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Silicate Phosphors From Sol-Gel Prescursors @ University of California-San Diego
9900034 Sailor This proposal is aimed at exploring the synthesis, chemistry and photophysics of a new class of silicate phosphor materials. The phosphors are unique in that no activator metals are needed to obtain efficient photoluminescence. Such materials may provide an alternative to existing phosphors that contain toxic heavy metal ions and as such pose a significant environmental hazard. The luminescent silicates that will be studied fall into two distinct classes depending on the alkoxysilane used in the synthesis. The first class are 'carboxysilicate' glasses that are stable at high temperatures. The second class are water-soluble 'aminosilicone' polymers that can be processed into a variety of shapes such as blocks, foams, and fibers. Both classes have high luminescence efficiency. These materials represent a new direction in silicon sol-gel chemistry and the aim of this proposal is to determine the structure, chemistry, and photophysics of the chromophore in these materials. %%% The discovery of efficient, environmentally benign phosphors for lighting, display, and specialty applications and the development of methods to synthesize polymeric silicones with interesting optical or electronic properties are of significant industrial interest as potential technologies.
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0.915 |
2000 — 2003 |
Fainman, Yeshaiahu [⬀] Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Chemical and Biological Sensors Based On Porous Silicon Photonic Micro-Systems @ University of California-San Diego
0088060 Fainman
There is a growing demand for the miniaturization of chemical and biological sensors for environmental, medical and security applications. Of great interest for such applications are low-power, compact, and cost effective micro-systems that combine non-electrical sensing capabilities and electronic processing. The goal of the proposed work is to conduct basic research towards the development of high sensitivity chemical and/or biological sensors integrated on a monolithic Si substrate. This multi-disciplinary study will focus on fundamental understanding of nano-scale chemical, biological and near-field optical interactions, leading to the development of design and implementation methodologies for porous silicon (Psi)-based sensor micro-systems. The proposed micro-systems will use optical transducers based on microfabricated optical sources combined with optimized nanostructured resonant optical filtering devices and photodetectors, allowing label-free detection of analytes with significantly higher sensitivity than existing techniques (e.g. surface plasmon resonance or optical interferometry). This technique will be applicable to a variety of sensing problems in environmental monitoring, medical diagnostics, high-throughput screening, and pharmacogenomics applications. The PIs propose to study two complementary aspects of this emerging technology: (a) investigation of the correlation between the modification of the optical properties of PSi and the concentration of different species introduced in the pores, including nerve agents, solvents, or biological molecules; and (b) design, modeling, fabrication and testing of monolithically integrated near-field meso-optic structures built using micro- and nano-fabrication techniques.
The proposed research will not only have a significant impact on the development of on-chip monolitically integrated micro-sensor systems, but also result in the development of basic science and technology of near-field linear and nonlinear optical phenomena in nano-scale and meso-scale structures. The proposed studies will also advance basic science and engineering in such multidisciplinary areas as vector field optical wave interactions in near-field nonlinear dielectric nanostructures, quantum and nonlinear optical processes in nanostructured composite materials, and fabrication of such devices using deposition, photochemistry, and ion implantation techniques. The proposed project will also play a unique role in the education and development of human resources in science and engineering at the graduate and undergraduate levels.
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0.915 |
2000 — 2002 |
Kavanagh, Karen (co-PI) [⬀] Rudee, M. Lea Schmid-Schoenbein, Geert Talbot, Jan Mckittrick, Joanna (co-PI) [⬀] Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Acquisition of a Cold Cathode Field Emission Gun Scanning Electron Microscope @ University of California-San Diego
This award from the Instrumentation for Materials Research program to the University of California San Diego is for the acquisition and installation of a cold cathode field emission gun scanning electron microscope(FEG-SEM) with analytical capabilities for the Electron Microscopy Facility of the Materials Science Program, part of the Jacobs School of Engineering at the University of California San Diego (UCSD). The new instrument will enhance existing and new research projects currently active at UCSD in the engineering, physics and chemistry departments, as well as at the Scripps Institute of Oceanography. The FEG-SEM will provide high beam stability, low energy fluctuation, low beam current and high brightness in a range of accelerating voltages, features that are required for imaging nanoscale features in electronic, magnetic, optical, structural, organic and biological materials. The instrument will enhance both graduate and undergraduate research and education. The graduate students will benefit from hands-on exposure to a state-of-the-art microscope that will aid significantly in their research projects. Undergraduates will particularly benefit from this class, as it will be offered to upper division students who have a materials emphasis in their major program (currently available in mechanical, electrical, physics and chemistry departments).
This award from the Instrumentation for Materials Research program to the University of California San Diego is for the acquisition and installation of a cold cathode field emission gun scanning electron microscope(FEG-SEM) with analytical capabilities for the Electron Microscopy Facility of the Materials Science Program, part of the Jacobs School of Engineering at the University of California San Diego (UCSD). The proposed equipment will replace the existing Cambridge 360 SEM, now 10 years old, and provide state-of-the-art capabilities. This system currently supports the research programs of faculty from departments and research units campus wide. The Materials Science Program will manage the new SEM and it will be available to all UCSD affiliated personnel and the outside community on an hourly fee basis.
The new instrument will enhance existing and new research projects currently active at UCSD in the engineering, physics and chemistry departments, as well as at the Scripps Institute of Oceanography (SIO). The FEG-SEM will provide imaging of detailed structures coupled with the elemental analysis capabilities; it is a crucial tool for modern materials research and for training the next generation of engineers and scientists.
The instrument will enhance both graduate and undergraduate research and education. The graduate and undergraduate students will benefit from hands-on exposure to a state-of-the-art microscope. A graduate level course in scanning electron microscopy will be introduced yearly into the Materials Science curriculum and will be available to all graduate students at UCSD and SIO. Undergraduates will particularly benefit from this class, as it will be offered to upper division students who have a materials emphasis in their major. In summary, the new instrument will provide a much-needed research and teaching tool by providing image and analytical capabilities not currently available to students on the UCSD campus.
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0.915 |
2005 — 2008 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Chemistry of Nanostructured Porous Si @ University of California-San Diego
This award from the Solid State Chemistry program in the Division of Materials Research to University of California San Diego is to develop an understanding of the effect of surface chemistry on the stability of porous silicon (Si) photonic crystals. With this award Professor Michael Sailor will probe the effects of chemical modification of the porous Si surface on its air and water stability using reactions designed to attach functional species via Si-Carbon bonds. Two related attachment chemistries would also be studied: electrochemical reduction of alkyl halides; and hydrosilylation of terminal alkenes. These chemistries have been found to impart remarkable stability to the porous Si surface relative to Si-H or Si-O surfaces. The fundamental question to be answered is: what is the reason for this improved chemical stability? A systematic study on the effect of pore dimensions, chain length of the organic modifier, surface coverage, and nature of the substituents on stability in air and aqueous media will be performed. The project should lead to new understanding of the reactivity of nanocrystalline silicon surfaces for potential applications in number fields.
In recent years there has been increased interest in developing low-power, miniature sensors that can be used to detect toxics, pollutants, or chemical and biological warfare agents in the environment. There is similar high interest in portable sensors that can be used to diagnose illness. One of the biggest challenges in this area is to place the sensitivity and specificity of a laboratory-scale instrument into a palm-top or smaller package. The goal of this research is to develop the chemistry of nanomaterials that can enable such applications, among others. Starting with crystalline silicon wafers, the same material used by the computer industry to build microchips, the project will build nanoscale structures that can act as sensors for chemical or biological compounds. The project should lead to a better understanding of the chemistry of silicon nanomaterials that will enable advances in the areas of medical diagnostics and therapeutics, remote sensors for pollution monitoring and homeland security applications, information display and optoelectronics. The primary product of this work will be to provide graduate and undergraduate students with a highly interdisciplinary education in materials chemistry and nanoscience. The students will be prepared for a variety of challenging research positions in the high-tech and biotech sectors of industry, government, and academia.
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0.915 |
2005 — 2007 |
Kastner, Miriam (co-PI) [⬀] Sasagawa, Glenn Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Exploratory Research: Evaluation of Porous-Silicon Sensors For Marine Science Applications @ University of California-San Diego Scripps Inst of Oceanography
The PIs propose to evaluate Porous Silicon (pSi) sensors for marine applications. Porous Silicon sensors will be fabricated and tested in a laboratory pressure cell, to simulate ocean pressures and temperatures. Optical nanostructures can be precisely fabricated in pSi sensors; the presence of an analyte will produce readily detectable changes in the nanostructure's optical properties such as the reflectivity spectrum. pSi sensors have been used on land to detect a number of chemical and biological signals, and have also been used in liquid solutions for biomedical applications. The PIs feel that pSi sensors could be developed for ocean science applications with the desirable qualities of inherent pressure tolerance, high sensitivity, small size, low power consumption and low cost. For this test, the chemical target will be methane, due to a) the importance of methane in the oceans, and b) the limitations of existing deep ocean methane sensors. There are significant unknowns concerning marine applications for pSi sensors, particularly biofouling and corrosion. The oceans will be a new and untested operating environment for pSi sensors.
Broader Impacts The PIs proposed to develop a new observational measurement technology for the ocean sciences. New ocean sensors would also have immediate applications in environmental monitoring and industrial processes. In addition, the proposed activity will provide training and education for graduate students and promote crossdisciplinary research.
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0.915 |
2005 — 2008 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nsf-Europe Materials Collaboration: New Functionalized Hybrid Systems For Drug Delivery @ University of California-San Diego
This award from the Solid State Chemistry program in the Division of Materials Research to University of California San Diego is to develop a chemically modified matrix of nanocrystalline porous Si or SiO2 to increase the high surface area and free volume at the nanoscale. Chemistries to cap the pores with noble metals, polymers, proteins, and silica derived from silanols will be studied, with the ultimate goal of developing a matrix for the slow release of drug under appropriate physiological conditions. The high surface area and free volume in porous Si films would allow the loading of a large amount of drug, and different drugs will be incorporated into these microscopic particles of porous Si. Delivering drugs to specified locations in the body at specified rates is an important aspect of effective medical therapies. The proposed work will encompass new methods of trapping molecules into porous nanostructures, and new methods of monitoring the porous nanostructures using the optical properties of the materials. In particular, one-dimensional photonic crystals will be prepared whose spectral signatures can report on the amount or type of drug contained within. This proposal, which was received at NSF in response to Materials World Network solicitation, is for collaborative efforts with European partners Drs. Bernard Coq, Jean-Marie Devoisselle and Frederique Cunin of the CNRS Laboratoire de Materiaux Catalytiques et Catalyse en Chimie Organique in Montpellier, France. The Montpellier lab has played a major role in the development and commercialization of liposome-based drug delivery materials in France. This collaborative program will bring together the drug delivery expertise of the Montpellier group with the nanomaterials design expertise of the UC San Diego research group.
The work will provide a highly interdisciplinary education to undergraduate, graduate, and post-doctoral students in the fields of nanotechnology, biotechnology, and pharmaceutical chemistry. Nanomaterials would be developed with this award with more sophisticated functions that could be used to more effectively deliver drugs to patients. The European collaborators of this project at the Montpellier laboratory had played a major role in the development and commercialization of liposome-based drug delivery materials in France. With this award, students will be involved in short-term and long-term exchanges and studies between the San Diego and the Montpellier labs.
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0.915 |
2008 — 2011 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Materials World Network: "New Functionalized Hybrid Systems For Biosensing and Drug Delivery" @ University of California-San Diego
The ability of molecules to navigate between membranes is key to many biological processes. For example, the transport of drugs across cell membranes often determines their efficacy. The objective of this project is to build artificial nanostructures to enable the study of the motion and concentration of molecules across interfaces, and to develop means to trap and release drug molecules within a nanostructure. The project investigates parameters that allow for the loading and the slow release of drugs under appropriate physiological conditions. The work encompasses new methods of trapping molecules into porous nanostructures, and new methods of monitoring the porous nanostructures using the optical properties of the materials.
The European partners in this effort are Drs. Frederique Cunin, Bernard Coq, and Jean-Marie Devoisselle of the CNRS Institut Charles Gerhardt, in Montpellier, France. The Montpellier lab has played a major role in the development and commercialization of liposome-based drug delivery materials in France, and the previous NSF-funded collaborative project has expanded the breadth of this effort significantly. The drug delivery and pharmaceutical characterization expertise of the Montpellier group combines with the nanomaterials design and optics expertise of the Sailor research group. The project features exchange of students between the two labs for durations of 2-4 months each year.
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0.915 |
2009 — 2010 |
Sailor, Michael J |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Photoluminescent Porous Si For Biological Applications @ University of California San Diego
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Different sizes of silicon particles with porous nanostructure and intrinsic photoluminescence are prepared and studied. Their low toxicity and biodegradability also give the particles great potential for biological applications. Using the photoluminescent porous Si particles for diagnostic and therapeutic applications are under study.
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1 |
2012 — 2016 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Materials World Network (Mwn): Chemistry of Porous Silicon Nanoparticles For Photodynamic Therapy @ University of California-San Diego
TECHNICAL SUMMARY: This collaborative project will combine the U.S. counterpart's expertise in silicon nanotechnology with the French counterpart's expertise in mesoporous drug delivery materials, photophysics, photodynamic therapeutic agents, and clinical photodynamic therapy on prostate cancer to develop photoactive anti-cancer materials based on biodegradable porous silicon nanoparticles. A main goal is to provide higher yields of singlet oxygen and/or reactive oxygen species to induce irreversible cell damage in the vicinity of cancer cells for more effective photodynamic therapy (PDT). The NSF-funded U.S. counterpart will focus on fundamental materials science issues: synthesis of porous Si nanoparticles with improved synthetic yields and PDT quantum yields, and development of optimal surface chemistries for PDT, biocompatibility, and targeting. The French funded counterpart lab will focus on the biological applications: targeting of nanoparticles inside cancer cells and one- and two-photon PDT in cancer cells.
NON-TECHNICAL SUMMARY: Photodynamic therapy (PDT), a treatment that combines the use of a sensitizing agent and light to kill cancer cells, has been in clinical use for over a decade. Despite the advantages of the therapy itself, photosensitizers in use today display toxic or other side effects that limit their use. The goal of the collaborative project is to combine the advantages of nanotechnology with photodynamic therapeutic agents to develop more effective anti-cancer materials and it will focus on biodegradable porous silicon nanoparticles The team from the U.S. includes graduate students, undergraduate students, and high school students. The effort will involve visits by U.S. and French students to the counterpart laboratories for month-long research experiences. The educational outreach activities will include a "Summer School for Silicon Nanotechnology," in which ten U.S. high school students will be hosted in the UCSD lab for one month every summer.
This project is supported by the Biomaterials program and the Office of Special Programs, Division of Materials Research.
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0.915 |
2014 — 2015 |
Anglin, Emily Jessica (co-PI) [⬀] Sailor, Michael J |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Modeling of the Vitreous For in Vitro Prediction of Drug Delivery of Porous Silicon Particles and Episcleral Plaques @ University of California San Diego
Abstract A significant limitation in the development of nanoparticle-based therapeutics is the lack of in vitro models that can predict in vivo behavior, in particular with respect to rate of release and steady state concentration of the therapeutic. This proposal focuses on development, testing, and validation of an in vitro device that can accurately predict therapeutic levels delivered from nanomaterials injected intravitreally or placed on the back of the eye. The testbed nanomaterial we will use is based on nanostructured porous silicon (pSi) and its composites with various biocompatible polymers. Porous silicon has been identified as an ideal drug carrier for ocular therapeutics. It has demonstrated excellent biocompatibility and biodegradability in vivo and versatile surface chemistry that enables incorporation of a wide range of drug types, including antibodies, oligonucleotides, and hydrophilic or hydrophobic small molecules. Although there has been significant progress in this area, testing candidate nanotherapeutic formulations in live animal eyes poses a challenge due to low drug levels in vitreous taps or expensive and time- consuming harvesting of the entire vitreous at each time point. For this proposal, we will design and construct a simulator that will mimic the vitreous to enable a more accurate correlation with in vivo drug release profiles than has been achieved previously. Formulations of pSi will be developed in collaboration with Spinnaker Biosciences, a small California company that has expertise in fabrication and testing of pSi particles for ocular therapeutics. Crosslinked hyaluronic acid and polyvinyl alcohol mixtures and copolymers will be used in conjunction with buffer solutions to imitate the viscous environment of the vitreous. Flow characteristics, viscosity, and temperature will be systematically varied for real-time and accelerated testing conditions. We will use a range of different pSi formulations to test nanoparticle degradation, dissolution, and drug release/leaching under a variety of experimental conditions. The results will be compared with in vivo tests of the same materials in rabbits. To provide additional correlative data, we will exploit the photonic properties of pSi to monitor its degradation and temporal drug release profile. The primary goal of the research is to develop a better understanding of the key in vitro characteristics needed to accurately mimic in vivo drug delivery in the eye.
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1 |
2016 — 2019 |
Sailor, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Porous Silicon Nanoparticle/Polycaprolactone Composite Nanofibers For Nervous System Repair @ University of California-San Diego
PI: Sailor, Michael J. Proposal #: 1603177
Nanofiber scaffolds have been used extensively in nerve regeneration strategies; however, current nanofiber technologies lack the ability to fully repair the injured nervous system, often due to difficulty in incorporating sensitive therapeutics into nanofibers caused by the volatile solvents that are used in their fabrication. The proposing group was the first to demonstrate the degradation of porous silicon nanoparticles to non-toxic silicic acid byproducts in-vivo and the first to demonstrate the ability of nanoparticles to be visualized in vivo using gated luminescence imaging. The goal of the proposed research is to build on these results by combining the advantages of porous silicon nanoparticles with polycaprolactone nanofibers, thus developing drug releasing composite nanofibers that can assist in increasing neurite outgrowth and improving nervous system repair. The nanoparticles provide protection of the therapeutics, enhance imaging potential and can be used to alter the degradation process. The nanofibers, whose alignment can be carefully controlled, provide a regenerative substrate that serves to enhance/direct the growth of extending neurites. In summary, if successful, the biodegradable nanofiber scaffolds, which can be easily tuned to alter scaffold degradation rate, photoluminescent intensity, therapeutic delivery, and substrate alignment, will provide an innovative and straightforward model for developing the next-generation of nanofiber scaffolds. Students involved in the research will be provided with a highly interdisciplinary education in materials chemistry, nanoscience, biomedical engineering, and biology. A capstone activity will be a 6-week summer school for silicon nanotechnology, involving high school, undergraduate, and graduate student mentors and mentees.
Nanofiber scaffolds have been used extensively in nerve regeneration strategies; however, current nanofiber technologies lack the ability to fully repair the injured nervous system, often due to difficulty in incorporating sensitive therapeutics (such as proteins, siRNA, etc) into nanofibers caused by the volatile solvents that are used in their fabrication. The goal of this three year project is to develop composite nanofibers, in which bioactive therapeutics can be incorporated, with the aim of creating customizable tissue engineering scaffolds for nervous system repair. The proposing group was the first to demonstrate the degradation of porous silicon nanoparticles to non-toxic silicic acid byproducts in-vivo, and the first to demonstrate the ability of nanoparticles to be visualized in vivo using gated luminescence imaging. The aim of this proposal will be accomplished by developing and systematically studying biodegradable porous Si/polycaprolactone composite fibers with a focus on engineering scaffolds for nervous system repair. The research is pursued under 4 main thrusts: 1) fabricate aligned or randomly oriented porous Si nanoparticle/polycaprolactone composite nanofiber scaffolds and determine photoluminescent properties and degradation of the scaffolds; 2) functionalize the surface of the porous Si/polycarpolactone nanofiber composites to improve cellular attachment and growth (including -OH and peptide functionalization) 3) incorporate and monitor release of bioactive therapeutics from the nanofiber composites that target the PI3K/Akt signaling pathway to enhance neurite extension (i.e. nerve growth factor, PTEN siRNA, and PTEN inhibitor) and 4) determine ability of nanofibers to enhance neurite extension (dosal root ganglion neurons)in vitro. Three key innovations of this research are the use of an airbrush method to fabricate nanofiber composites, utilizing photolumiscent properties of porous Si nanoparticles to monitor degradation of the composite scaffolds, and incorporating sensitive therapeutics into nanofiber composites to enhance neurite extension. If successful, the approach will have applications in medical therapeutics, tissue engineering, and implantable scaffold imaging and broadly impact research areas of implantable biomaterials, MEMS, and controlled drug release. Students involved in the research will be provided with a highly interdisciplinary education in materials chemistry, nanoscience, biomedical engineering, and biology, in preparation for a variety of challenging research positions in the biotech sectors of industry, government, and academia. A capstone activity will be a 6-week summer school for silicon nanotechnology, involving high school, undergraduate, and graduate student mentors and mentees.
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0.915 |
2017 — 2021 |
Bhatia, Sangeeta N. (co-PI) [⬀] Sailor, Michael J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Infection-Homing Osystems as Antibacterial Therapeutics-Delivery Platforms @ University of California, San Diego
PROJECT SUMMARY Staphylococcus aureus and Pseudomonas aeruginosa are the leading causes of hospital-acquired infections and contribute significantly to morbidity and mortality [3, 4]. Standard treatment of infection entails repetitive high-dose administrations of antibiotics, but the treatment is often rendered ineffective due to poor delivery to sites of infection and drug resistance mechanisms preventing antibiotic access to intracellular drug targets (e.g. the drug-impermeable cell wall in gram-negative P. aeruginosa) [5, 6]. Skin infections that have invaded down to the muscles and fibers are also difficult-to-reach by free-antibiotic formulations and require surgical treatment [7]. The obstacles we tackle in this proposal are: (1) loss of antibiotics to non-infected tissues; (2) rapid clearance of small molecule antibiotics by renal and gastrointestinal clearance; (3) poor penetration of drugs past the bacterial cell wall. We hypothesize that loading antibiotics into longer-circulating nanovehicles that will home to sites of infection and subsequently facilitate drug uptake into cells/bacteria of interest can overcome the abovementioned challenges. Here, we propose to develop such nanoplatforms through three major aims. In Aim 1, we will use in vivo phage display to identify peptides that will home to the bacteria of interest and/or infected tissue. We will focus specifically on S. aureus and P. aeruginosa infections in models of deep skin (invasion in muscles and fibers) infection and pneumonia in mice. In the event that direct bacteria- targeting proves to be difficult, we will also look at peptides that bind selectively to infected tissues and host cells surrounding the bacterial colonies, as well as macrophage-targeting peptides. As these peptides are to be conjugated to nanoparticle surfaces, we will then investigate the binding properties of the peptides in singular and multivalent forms. In Aim 2, we will engineer two nanoplatforms: (1) peptide-based agents that can selectively penetrate the bacterial membrane (i.e. peptide permeation agents) to which small molecule drugs will be tethered for increased uptake and (2) porous silicon nanoparticles (pSiNP) to load drugs that have poor delivery to sites of infection due to unfavorable physicochemical properties (hydrophobic, highly ionic, etc). These nanoplatforms will be targeted to sites of infection using peptides we have previously discovered or additional peptides to be identified in Aim 1. Model drugs with poor in vivo antibacterial activity will be loaded and optimal platforms selected based on drug loading, release kinetics, and cellular uptake for in vivo pharmacokinetics. In addition to individual pSi- and peptide-based nanoplatforms, we will develop a combined system in which bacteria-penetrating drug conjugates are loaded into targeted pSi nanoparticles with the goal of enhanced efficacy. Finally, Aim 3 will focus on the therapeutic performance of lead nanoplatform candidates in vivo. The goal of this aim is to demonstrate the biosafety and therapeutic efficacy (i.e. bacterial burden clearance, tissue recovery, improved survival) of the pSiNP and bacteria-penetrating nanosystems. This project will yield tools to actively target infected tissues as well as a strong set of nanoplatforms that can address many of the current barriers to in vivo antibacterial drug activity.
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1 |
2020 — 2026 |
Sailor, Michael Meng, Ying (co-PI) [⬀] Tao, Andrea (co-PI) [⬀] Steinmetz, Nicole (co-PI) [⬀] Pokorski, Jonathan |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Uc San Diego Mrsec: An Nsf Materials Research Science and Engineering Center @ University of California-San Diego
Nontechnical Abstract: The growth, prosperity, security, and quality of life of humans are in large part determined by the materials they use. The mission of the UC San Diego Materials Research Science and Engineering Center (UCSD MRSEC) is to perform innovative, interdisciplinary materials research relevant to societal needs, and to prepare students to become future leaders in materials design and discovery. The research effort of the Center is conducted within two highly interdisciplinary groups. The first group is deploying the most powerful computers available to understand, predict, and ultimately control the properties of materials at microscopic size scales?sizes just larger than molecular dimensions. It is in this size regime where many useful properties of materials emerge. For example, changes in the shape of metal particles at this scale can change their color, their efficiency as a catalyst, or their sensitivity in a medical diagnostic test. The second group is using the tools of the biotechnology revolution?in particular, genetic engineering and synthetic biology?to build new classes of materials that can respond to stimuli from their environment in useful ways. Both groups are targeting fundamental breakthroughs that can impact a number of critically important needs: faster, more accurate sensors for medical diagnostic tests, more efficient decontamination of chemical or biological hazards, better catalysts to reduce the cost of industrial processes, and improved therapeutics for treating diseases. The fundamental research within the two groups is empowered by an integrated educational program to prepare a diverse community of trainees to enhance national proficiencies in the science, technology, engineering, and mathematics fields. Immersive training for scientists across all levels ? novice through established ? develops technical competency in laboratory procedures, advanced instrumentation, and computational methods. Internship and scientist-in-residence programs fuel vital exchange of ideas and leverage partnerships with industry, national laboratories, and other collaborators. Partnership with the Fleet Science Center builds researchers? skills in science communication and connects the UCSD MRSEC with the diverse San Diego community to address community-articulated needs.
Technical Abstract: The UCSD MRSEC addresses two fundamental challenges: (1) How to predict and direct the assembly of materials at the mesoscale, where macroscopic behavior and properties emerge (IRG1: Predictive Assembly); and (2) How to deploy the tools of synthetic biology to build soft materials that meld the characteristics of living systems with the performance requirements of advanced engineered materials (IRG2: Stimuli-Responsive Living Polymeric Materials). IRG1 focuses on the rational design of innovative, functional mesomaterials with programmed plasmonic, catalytic, and structural properties. A computation-driven framework is being created to understand, predict, and design how shaped nanocomponents are used as material building blocks. The models developed bridge length and time scales relevant to mesoscale assembly. IRG2 integrates engineered living matter ? photosynthetic organisms ? into biological composites that respond to stimuli with genetically encoded outputs, such as chemical reagents and polymer feedstocks. The UCSD MRSEC creates unique resources to benefit the broader materials-research community: a MesoMaterials Design Facility ? a virtual, computational facility, and an Engineered Living Materials Foundry, consisting of a bio-synthesis laboratory and soft-matter characterization tools. The Center?s educational goals include preparing the next generation of interdisciplinary materials scientists, and increasing diversity and inclusion in materials research. The Research Immersion in Materials Science and Engineering (RIMSE) Summer Schools provide intensive training in the areas of IRG research. Enabling professional development for Center members in science communication, a partnership with the Fleet Science Center facilitates meaningful engagement with the diverse San Diego community.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.915 |