This award by the Biomaterials program in the Division of Materials Research to New Mexico State University, Las Cruces is to develop and evaluate unique properties of a new class of hybrid nanomaterials and to study hydrophobicity switching process in nanoporous materials. Hydrophobicity is a fundamental property that is responsible for numerous physical and biophysical behaviors of nonpolar substances in water. This water-induced effective attraction between nonpolar molecules is called the hydrophobic interaction. The interplay between hydrophobic and hydrophilic properties is due to conformational changes in biologically important molecules and is responsible for many of their biochemical functionality, such as stability and penetration of bilipid cell membranes, protein folding and misfolding, DNA-protein interaction and many other related phenomena. This project will study the hydrophobicity switching in response to various physical and chemical stimuli for possible regulation of molecule and ion transport through lipid bilayers or cell membranes. A systemic study of hydrophobic switching will be carried out to understand the release of intracellular release of molecules including drugs in response to their high concentrations using two types of nanopores, namely, hydrophobic nanoporous membranes and hydrophobic nanotubes. In addition, the proposed model for a new drug delivery mechanism will be evaluated that could avoids endocytosis and thus avoiding many side effects during intracellular drug delivery.
The proposed project is expected to develop an understanding of how to control hydrophobicity and transport of molecules and ions through hydrophobic nanopores, and this knowledge base is critical in the development of novel drug delivery systems. The use of hybrid nanomaterials and bio-inspired approaches in these applications offers the possibility of innovative solutions that are not only versatile, but also cost effective, robust and environmentally benign. The New Mexico State University at Las Cruces is a Hispanic-serving institution, and the PI plans to continue recruiting, teaching and training students (graduate, undergraduate and high school), especially underrepresented minority students including women and Hispanic students. In addition, web-based education, recruiting and training students for Chemical Olympics and Chemical Education are some of the other planned outreach activities.
We have illustrated that small sized pores (nanopores) that have hydrophobic interior possess unique physico-chemical properties that, among other applications, can be employed as novel hybrid nanomaterials for drug delivery. The unique behavior is driven by the ‘desire’ of hydrophobic nanopores to stay dry in water and aqueous solutions. There are different means of counteracting this behavior such as applying pressure or by altering the surface properties to make it more hydrophilic. The latter approach, hydrophobicity switching, can be made responsive to various physical and chemical stimuli and thus mimic the ion channels for transport of molecules and ions. We have illustrated how it can be responsive to pH, light, the electrical potential, and some small molecules. A very promising biomimetic design for nanomaterials that utilizes this hydrophobicity switching behavior can be employed in drug delivery, which we have been trying to elucidate in this study. Hydrophobic nanopores can be loaded with molecular and biomolecular cargo molecules by using low surface tension solvents, e.g. alcohol. After drying, when immersed in water, the hydrophobic entrance keeps cargo from leaking into the water but high concentrations of amphiphiles, such as cellular membrane phospholipids, can switch off the hydrophobic entrance by assembling at the walls and thus release the cargo. Such as a release can actually be accompanied by creation of a hole in the phospholipid membrane and thus realize a pathway in which the carrier is not required to enter the cell. The latter is a potential advantage as minimal harm would be introduced by the delivery system itself. We have designed a drug delivery system using silica nanotubes with hydrophobic interior that can target specific cancerous cells. Folic acid receptors are over expressed (produced in excessive quantities) on the surface of many cancerous cells, such as some forms of cervical cancer, breast cancer, and others. We have equipped our hydrophobic silica nanotubes with folic acid ligands on their exterior to target such cancerous cells and illustrated that significantly greater amount of cargo was internalized by the targeted cells than by nontargeted. The outcome is also sensitive to other properties of the surface modification of the nanotubes, as well as their dimensions, and is the topic of continuing studies. The research represents new viable strategies for combining material, surface, chemical and biological sciences for the design of new bioinspired nanomaterilas. Three graduate and two undergraduate students were involved in the project and were trained on variety of new techniques. Two students were granted PhDs. The PI has also contributed to conducting a competition for high school students on the subject of chemistry (Chemical Olympics), in which students from New Mexico, Texas and Arizona had participated.
