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.
The objective of the work was to develop a fundamental understanding of the interactions of molecules with porous nanomaterials, discover new methods to probe these interactions, and ultimately design into the nanomaterials an ability to hold and release drug molecules under precisely specified conditions. The materials focus was on silicon-based optical nanostructures prepared by electrochemical etch of crystalline silicon wafers. The European partners for this effort were Drs. Frederique Cunin, Bernard Coq, and Jean-Marie Devoisselle of the CNRS Institut Charles Gerhardt, in Montpellier, France. This group is expert in development and characterization of drug delivery materials. Major Research Accomplishments During the funding period we published 20 papers citing this grant; three of the most important highlights are given below: (1) Self-Reporting Nanoreactor This advance focused on the problem of manipulating and processing small quantities of biological matter—the front end of a device that in the future may be sitting in a doctor’s office or in a patient’s home helping to identify biological indicators of disease. The nano-reactor processes very small (nanoliter) quantities of material and consists of two porous layers—a reactor layer and a layer that receives the products of the reaction. The synthesis we developed for these layered structures is an example of a top-down approach used to make nanomaterials. The silicon nanostructure is made using electrocorrosion, which removes atoms from the silicon wafer in a very controlled fashion. Corrosion is what causes your car to rust—it converts the iron to iron oxide. Electrocorrosion of silicon can be used to generate very well-defined porous nanostructures. Figure 1 shows a cross-sectional view of a nanoporous layered structure that we carved from a solid crystal of silicon using this approach. (2) Spectral Barcodes In the course of our studies of the optical properties of porous silicon nanostructures, we developed a method to encode the particles with specific spectral signatures. The application of these materials as non-toxic tags for pharmaceuticals was licensed to Cellular Bioengineering, inc., who markets this invention under the TruTag trademark (www.trutags.com). (3) Carbon/Silicon Composite Sensors Templated in Porous Silicon Photonic Crystals. The first line of defence against the presence of airborne pollutants and toxic chemicals is a respirator containing a carbon filter – a "gas mask." One way to improve the safety of first responders and other respirator users is to incorporate tiny sensors that detect the presence of chemicals. Sensors embedded in a respirator could alert the user when the carbon filter nears its full capacity and needs to be changed. Our group developed just such a sensor. The sensors are based on a type of material known as a photonic crystal – these special materials have repeating structures that cause them to reflect light of specific colors, or wavelengths. Our team developed a method to assemble photonic crystals from carbon nanowires. Normally this form of carbon is black, but in the photonic crystal form, the nanowires display a characteristic color. The carbon nanowires have the same chemical properties as the activated charcoal used in respirators, so the colored nanowires have a similar capability to absorb organic pollutants. However, unlike the carbon used in a respirator, our photonic carbon changes color when it absorbs these toxins—therefore the carbon nanowires provide a visible signal indicating how much they have absorbed, and, more importantly, how much capacity for additional chemicals remains. Personnel and Human Resources: The five graduate students involved in this project directed a total of 10 undergraduate students through the course of their Ph.D. thesis work, all of whom have gone on to graduate school, pharmacy school, or medical school. All of the graduate students visited the counterpart labs in Montpellier during the course of their PhD studies. In addition, two French graduate students from Montpellier worked on their thesis projects in the UCSD labs. In addition to the graduate students described above, the PI sponsored and supported 2 high school students per year in his lab during the project period; the two most recent of these (Anna Kornfeld Simpson and Carrie Cao) won the top prizes in the California State Science Fair for their age groups in 2009 and 2010, respectively. Simpson and Cao were both semifinalists in the 2010 and 2011 Intel Science Talent Search, respectively. To our knowledge, Prof. Sailor’s lab is the only University lab in the U.S. to ever host high school students who went on to be back-to-back semifinalists in the Intel STS. This past year Ms Cao won 8th place overall in the Intel STS (Figure 2). She was the only one of 40 semifinalists from San Diego county. SeeNSF ScienceLives, www.livescience.com/culture/090819-sl-sailor.html As a culmination of Dr. Sailor’s outreach activities, this past summer he hosted ten high school students in his lab in a "Summer School for Silicon Nanotechnology," see Figure 3.
