Author : Mike Jeon
Publisher :
ISBN 13 :
Total Pages : 131 pages
Book Rating : 4.:/5 (112 download)
Book Synopsis Iron Oxide Nanoparticles for Targeted Cellular Imaging and Drug Delivery by : Mike Jeon
Download or read book Iron Oxide Nanoparticles for Targeted Cellular Imaging and Drug Delivery written by Mike Jeon and published by . This book was released on 2019 with total page 131 pages. Available in PDF, EPUB and Kindle. Book excerpt: Iron oxide nanoparticles (IONPs) have drawn significant interest in the field of biomedicine due to their intrinsic magnetic properties that allow contrast under magnetic resonance imaging (MRI). With proven biocompatibility, biodegradability, and flexible surface chemistry for a variety of applications, IONPs have been used as theranostic agents, combining therapy and diagnosis in a single formulation. Despite their potential, few IONPs have transitioned to the clinic due to the challenges of achieving high drug loading while maintaining proper size and stability to bypass biological barriers, minimizing off-target drug release to prevent side effects, and increasing specificity to minimize non-specific uptake for increased efficacy. Many strategies can overcome these limitations. To increase specificity, incorporating active targeting by conjugating targeting agents onto IONPs can specifically bind and label intended sites. This approach can open up labeling and imaging of novel sites, such as neurons, when using MRI for diagnostic purposes. For drug delivery purposes, chemotherapeutics can be loaded onto IONPs with controlled release to prevent drug leakage and the consequent side effects. Incorporating targeting agents can further reduce off-target drug release. While IONPs have historically seen great utility as T2 contrast agents, these applications could be further expanded by designing IONPs for T1 contrast enhancement. This dissertation documents the development of iron oxide nanoparticle systems intended to overcome the shortcomings of various iron oxide nanoparticle applications with novel applications. First, we used IONPs conjugated with a dopaminergic neurolabeler to actively target the dopamine transporter to label and image dopaminergic neurons under MRI. The neurolabeler enhanced targeting and uptake of IONPs 3-fold over control IONPs. Labeling and imaging the brain using PET/SPECT is a tool to diagnose neurological disorders, such as Parkinson's disease. By using IONPs, this technique can be expanded to MRI to improve upon the shortcomings of PET/SPECT. Next, IONPs were loaded with paclitaxel to treat breast cancer cells. Due to their severe hydrophobicity, paclitaxel were bound close to the core of the IONP via an acid-cleavable ester bond, with longer chain PEG providing steric stabilization and hydrophilicity to stabilize the IONP. The paclitaxel loaded IONPs were further modified with folic acid, used as a targeting agent to bind to the folate receptors that are commonly over-expressed in breast cancer cells. The folic acid labeled and paclitaxel loaded IONP enhanced uptake by 2-fold, demonstrated controlled release of paclitaxel, and produced significantly higher cytotoxicity in breast cancer cells compared to free paclitaxel. Despite their proven efficacy as T2 contrast agents, IONPs have been hindered in their translation to clinical imaging applications due to the inherent limitations of T2 contrast agents. The benefits of T1 contrast has led to gadolinium-based contrast agents (GBCAs) serving as the dominant contrast agents in the clinic, while their severe side effects have highlighted the need for a biocompatible alternative. IONPs have the ability to serve as an alternative T1 contrast agent to GBCAs, but their potential has not been fully explored. Using the fundamentals of T1 contrast, we developed and characterized a T1 IONP. It demonstrated excellent physiological properties ideal for biological applications, with T1 contrast capabilities confirmed through phantom MR imaging. Finally, with clinical translation in mind, we investigated optimization of freeze-drying methods to prolong the stability of IONPs. Aqueous solutions can hydrolyze and degrade NPs, prohibiting long-term stability in solutions. Freeze-drying offers means of removing water to prevent degradation, yet freeze-drying stresses can cause irreversible damage to NPs. Cryoprotectants have been used to minimize or rid these freeze-drying stresses, yet their effects on IONPs have not been explored. A variety of cryoprotectants were tested for their effects on maintaining size, stability, zeta potential, and magnetic properties after freeze-drying on IONPs produced by the Zhang group and commercially available IONPs. Sucrose was the most effective cryoprotectant, with 10 wt.% sucrose offering IONPs great stability up to 6 months while preserving size, zeta potential, and magnetic properties.
