The goal of this research is to study properties of organic nanoparticles secreted from English ivy (Hedera helix), and develop a nature-based organic nanoparticle for biomedical applications. It was recently discovered by the PI that ivy secretes nanoparticles for surface affixing. The adhesive force from the combination of the ivy nanoparticles and the mucopolysaccharide secreted from ivy has been demonstrated in the literature to be one of the largest forces per area in natural surface adhesion. By characterizing the role and discovering the chemical structure of the ivy adhesive nanoparticles, we will develop a nature-based nanoparticle for medical adhesive. Previous research undertaken by the PI regarding ivy nanopartciles has led to a prototype method to isolate the ivy nanoparticles, and to determine the adhesive strength of the nanoparticles using atomic force microscopy. These studies indicated that the adhesive had properties that could be translated into a nature-based nanoparticle for medical adhesive. This proposal aims to advance the preliminary studies, to completely characterize the nanoparticles, to understand toxicity of the nanoparticles and to investigate a prototype approach for synthesizing the ivy nanoparticles. The specific aims of this research are to 1) isolate nanoparticles from aerial rootlets of English ivy, 2) characterize the adhesive properties and toxicity of the ivy nanoparticles for medical applications, and 3) investigate a prototype approach for synthesizing the ivy nanoparticles.
Intellectual Merit: A great amount of research is currently being undertaken on the use of nanoparticles for a variety of biomedical applications including targeted drug delivery, molecular imaging and high strength biomaterials. By biomimicking the role of ivy nanoparticles for adhesive, this research introduces the first nature-based organic nanoparticle that can be used for a variety of biomedical applications including medical adhesive, sunscreen cancer prevention and targeted drug delivery. At present, nearly all nanoparticles synthesized are metal nanoparticles that have inherent toxicity in mammalian systems. A biological nanoparticle will be able to avoid much of the toxicity associated with metal-based nanoparticles and expand the application of nanoparticles to medicine. In addition, this research will provide a protocol approach for isolating nanoparticles from a variety of biological species including ivy, sundew and marine mussels. Finally, this research will contribute to the development of nanoparticle enhanced polymers for high strength nanocomposites, and provide useful information on a biological method for creating nanocomposite for strong adhesives.
Broader Impacts: This research has broad impacts on biomaterial design through biomimetics, naturebased organic nanoparticle manufacturing and biomedical applications of nanoparticles for skin cancer prevention as well as drug delivery. Pharmaceutical fields have long recognized the importance of observing natural processes, to find the simplest and the most efficient way to develop drugs. Biomedical engineering is turning to biomimetics for finding ways to synthesize and develop complex nanostructure and devices for medicine. The fields benefitted by this research include material sciences, molecular biology, plant biology, bioengineering and nanomedicine. The results of this research will be used to extend our departmental curricula into nanomedicine and biomimetics for biomedical engineering innovation, and to be integrated into one of the core biomedical engineering graduate courses entitled nano bio-systems and biomimetics. This project will also be used as a foundation for local educational outreach in middle and high schools, and to draw interest into interdisciplinary sciences at early ages. Already these studies have encouraged both graduate students and undergraduates working in the labs to take interdisciplinary courses. We expect to develop an interdisciplinary curriculum across the university with the goal of training an interdisciplinary core of researchers. The PI's lab commits strongly to minority student training.
The outcomes of the plant-based portion of the NSF project was to elucidate the mechanism in which nanoparticles are produced by English ivy roots, innovate a nanoparticle production method from these plants in culture vessels, partially characterize the chemical composition of the particles, and perform experiments to describe some key physico-chemical properties. Nonoparticles are produced by adventitious roots in which root hairs play an important role in biosynthesis. Using manipulations of auxins and other plant tissue culture conditions and specialized vessels, we were able to produce nanoparticles in relatively pure form up to 90 mg of dry particles per 12 g of roots. The nanoparticles are aparently compsed of glycoproteins for which we have identified some candidate proteins that provide a match to the expressed gene sequence. Finally, the nanoparticles have interesting UV blocking properties that make them good sunscreen candidates. Taken altogether, Engilish ivy nanoparticles can now be efficiently produced to relatively high levels that can be tested for commercial properties. Most important, since the nanoparticles appear to be proteins, we now have the tools to efficiently search sequence dataspace for the respective genes. These are the first instance of the characterization of proteinaceous nanoparticles produced naturally in plants. Last Modified: 12/03/2013 Submitted by: Neal Stewart We have characterized physicochemical properties of the ivy nanoparticles, and used the ivy nanoparticles for drug delivery as well as tissue engineering. Results from this study demonstrated that, the ivy nanoparticles are non-toxic, and can be safely used for biomedical applications. After treatment at 100 °C, there was an increase in the UV extinction spectra of the ivy nanoparticles caused by the partial decomposition. The UVA extinction spectra of the ivy nanoparticles gradually reduced with the decrease of pH values in solvents. Prolonged UV irradiation indicated that the influence of UV light on the stability of the ivy nanoparticle was limited and time-independent. The above results demonstrated ivy nanoparticles' potential as an alternative to replace metal oxide nanoparticles in sunscreen applications. For drug delivery, we found that the ivy nanoparticles could promote the nucleus delivery of doxorubicin and hence increase the killing effect. By biomimicking the role of ivy nanoparticles for adhesive, we found the ivy nanoparticles could enhance cell binding in nano-scaffolds, which may be further used in tissue engineering for cell attachment. The protocol approach for isolating nanoparticles developed throgh this research has been used in isolating nanoparticles from sundew and fungus. We are currently working to develop nanoparticle enhanced high strength medical adhesive. This research has clear impacts on biomaterial design through biomimetics, and greenly manufacturering nanoparticles using plants. The results of this research has been integrated into our core biomedical engineering graduate courses entitled nano bio-systems and biomimetics. Two PhD students partially supported by this project have graduated. One of them was a female PhD student in biomedical engineering.