VTechWorks staff will be away for the winter holidays starting Tuesday, December 24, 2024, through Wednesday, January 1, 2025, and will not be replying to requests during this time. Thank you for your patience, and happy holidays!

Browsing by Author "Grove, Tijana Z."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Developing Photo-responsive Metal-Organic Frameworks towards Controlled Drug Delivery
    Epley, Charity Cherie (Virginia Tech, 2017-07-14)
    The development of therapeutic drugs or drug systems that enhance a cancer patient's quality of life during treatment is a primary goal for many researchers across a wide range of disciplines. Many investigators turn to nanoparticles (~50-200 nm in size) that tend to accumulate in tumor tissues in order to deliver active drug compounds to specific sites in the body. This targeted delivery approach would reduce the total body effects of current cancer drugs that result in unwanted (sometimes painful and even fatal) side effects. One of the main obstacles however, is ensuring that drugs incorporated into the nanoparticles are anchored such that premature drug release is prohibited. Also, while it is important to ensure strong drug-nanocarrier interactions, the nanocarrier must be able to release the drug when it has reached its biological target. We have developed a nanocarrier that provides a platform for drug systems that could achieve this drug release via the use of a light "trigger". Metal-Organic Frameworks (MOFs) are a relatively new class of often highly porous materials that act as "sponges" for the absorption of various small molecules. MOFs are so named because they consist of metal clusters that are linked by organic compounds to form networked solids that are easily tuned based on the choice of metal and organic "linker". We have developed a MOF nanocarrier incorporating benign zirconium (IV) metal clusters bridged by an organic component that changes shape when illuminated with a light source. The resulting material is therefore not stable upon irradiation due to the organic linker shape change that disturbs the MOF structure and causes it to degrade. When loaded with drugs, this photo-enhanced degradation results in the release of the cargo thereby, providing a handle on controlling drug release with the use of a light trigger. We have demonstrated that in the presence of the MOF nanocarrier incorporating 5-fluorouracil (a clinically available cancer drug), very low toxicity to human breast cancer cells is observed in the dark, however, cell death occurs in the presence of a light source. These reports offer a model MOF nanocarrier system that could be used to incorporate various drugs and therefore tune the system to an individual patient's needs. Furthermore, we also developed a material that is capable of providing magnetic resonance imaging (MRI) contrast by changing the metal to manganese (II). MRI contrast agents are compounds that serve to either darken or brighten an MRI image based on the agent used and therefore they aid in clinical diagnosis by making internal abnormalities easier to spot. Currently gadolinium (III) complexes are the most widely used contrast agents; however, the toxicity of gadolinium (III) has been shown to be responsible for the development of nephrogenic systemic fibrosis in some patients. This manganese material has also shown useful for the attachment of fluorescent dyes that can aid in the benchtop optical diagnosis of biopsies. These reports provide a basis for developing ways to offer controlled drug delivery in cancer patients and to aid in cancer diagnosis using MOF materials, in an effort to reach the goals of comfortable cancer treatment.
  • Thumbnail Image
    Development of Metal-based Nanomaterials for Biomedical Applications
    Roth, Kristina L. (Virginia Tech, 2017-04-21)
    New synthetic advances in the control of nanoparticle size and shape along with the development of new surface modifications facilitates the growing use of nanomaterials in biomedical applications. Of particular interest are functional and biocompatible nanomaterials for sensing, imaging, and drug delivery. The goal of this research is to tailor the function of nanomaterials for biomedical applications by improving the biocompatibility of the systems. Our work demonstrates both a bottom up and a post synthetic approach for incorporating stability, stealth, and biocompatibility to metal based nanoparticle systems. Two main nanomaterial projects are the focus of this dissertation. We first investigated the development of a green synthetic procedure to produce gold nanoparticles for biological imaging and sensing. The size and morphology of gold nanoparticles directly impact their optical properties, which are important for their function as imaging agents or their use in sensor systems. In this project, a synthetic route based on the natural process of biomineralization was developed, where a designed protein scaffold initiates the nucleation and subsequent growth of gold ions. To gain insight into controlling the size and morphology of the synthesized nanoparticles, interactions between the gold ions and the protein surface were studied along with the effect of ionic strength on interactions and then subsequent crystal growth. We are able to control the size and morphology of the gold nanoparticles by altering the concentration or identity of protein scaffold, salt, or reducing agent. The second project involves the design and optimization of metal organic framework nanoparticles for an external stimulus triggered drug delivery system. This work demonstrates the advantages of using surface coatings for improved stability and functionalization. We show that the addition of a polyethylene glycol surface coating improved the colloidal stability and biocompatibility of the system. The nanoparticle was shown to successfully encapsulate a variety of small molecule cargo. This is the first report of photo-triggered degradation and subsequent release of the loaded cargo as a mechanism of stimuli-controlled drug delivery. Each of the aforementioned projects demonstrates the design, synthesis, and optimization of metal-based systems for use in biomedical applications.
  • Thumbnail Image
    Protein-aided formation of triangular silver nanoprisms with enhanced SERS performance
    Geng, Xi; Leng, Weinan; Carter, Nathan A.; Vikesland, Peter J.; Grove, Tijana Z. (Royal Society of Chemistry, 2016-05-10)
    In this work, we present a modified seed-mediated synthetic strategy for the growth of silver nanoprisms with low shape polydispersity, narrow size distribution and tailored plasmonic absorbance. During the seed nucleation step, consensus sequence tetratricopeptide repeat (CTPR) proteins are utilized as potent stabilizers to facilitate the formation of planar-twinned Ag seeds. Ag nanoprisms were produced in high yield in a growth solution containing ascorbic acid and CTPR-stabilized Ag seeds. From the time-course UV-Vis and transmission electron microscopy (TEM) studies, we postulate that the growth mechanism is the combination of facet selective lateral growth and thermodynamically driven Ostwald ripening. The resultant Ag nanotriangles (NTs) exhibit excellent surface enhanced Raman spectroscopy (SERS) performance. The enhancement factor (EF) measured for the 4-mercapto benzoic acid (4-MBA) reporter is estimated to be 3.37 × 105 in solution and 2.8 × 106 for the SERS substrate.
  • Thumbnail Image
    Seed-mediated biomineralizaton toward the high yield production of gold nanoprisms
    Geng, Xi; Roth, Kristina L.; Freyman, Megan C.; Liu, Jianzhao; Grove, Tijana Z. (Royal Society of Chemistry, 2016-07-12)
    Gold nanotriangles (Au NTs) with tunable edge length were synthesized via a green chemical route in the presence of the designed consensus sequence tetratricopeptide repeat (CTPR) protein, halide anions (Br−) and CTPR-stabilized Ag seeds. The well-defined morphologies, tailored plasmonic absorbance from visible-light to the near infrared (NIR) region, colloidal stability and biocompatibility are attributed to the synergistic action of CTPR, halide ions, and CTPR-stabilized Ag seeds.