Title:
Development of polymer-coated nanoparticle imaging agents for diagnostic applications

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dc.contributor.advisor Nie, Shuming
dc.contributor.author Kairdolf, Brad A. en_US
dc.contributor.committeeMember Bao, Gang
dc.contributor.committeeMember Murthy, Niren
dc.contributor.committeeMember Varma, Vijay
dc.contributor.committeeMember Wang, Zhong Lin
dc.contributor.department Biomedical Engineering en_US
dc.date.accessioned 2010-01-29T19:57:43Z
dc.date.available 2010-01-29T19:57:43Z
dc.date.issued 2009-11-12 en_US
dc.description.abstract While significant progress has been made in the treatment and management of cancer, challenges remain because of the complexity and the heterogeneous nature of the disease. The improvement that has been seen in survival rates reflects advancements not only in treatment, but also in early stage detection and diagnostics for certain cancers. In particular, early stage detection and treatment of cancer before it has metastasized to other organs has resulted in a dramatic improvement in patient survival rates. One area of research that has shown considerable promise in further advancing diagnostics and early cancer detection is nanotechnology. Specifically, semiconductor and metal nanoparticles have great potential to provide advanced technology platforms for ultrasensitive and multiplexed detection of disease markers and probe disease on the molecular level. Because they are in the same size regime as biological molecules, these nanoparticles exhibit unique interactions with proteins, nucleic acids and other biomarkers of interest for detecting and diagnosing disease. However, high-quality nanoparticles are often unsuited for use in complex biological environments because of their coatings and surface chemistry. In this work, we describe the design and development of polymer-coated nanoparticle imaging agents for use in blood, cell and tissue diagnostic applications. Low-molecular weight, amphiphilic polymers capable of noncovalent interactions with nanoparticle surface ligands and the aqueous environment were synthesized and characterized for use in nanoparticle coating applications. We demonstrate that the hydrophobic and hydrophilic interactions between the nanoparticle surface, the amphiphilic polymer and the aqueous solvent were able to drive the coating and water solubilization of quantum dots. Novel nanoparticle synthetic techniques were also developed using the amphiphilic polymers in a one-pot method to make high quality semiconductor and gold nanoparticles and stabilize and encapsulate the particles for transfer into water. Using the polymer functional groups as multidentate ligands, nanoparticles were synthesized with a high degree of size control and increased stability. In addition, by performing the synthesis in a noncoordinating amphiphilic solvent such as polyethylene glycol, nanoparticles were immediately transferred to water with the excess polymer forming a water soluble coating. Next, nanoparticle surface charge and how it relates to the nonspecific binding of nanoparticles in cells, tissues and other complex biological samples was studied. We have found that highly charged (negative and positive) particles exhibit significant nonspecific binding to biomolecules and other cellular components in biological environments. By reducing the surface charge through the incorporation of hydroxyl functional groups, we have nearly eliminated the nonspecific binding of quantum dots in blood, cells and tissues. Moreover, through crosslinking and altering the surface chemistry of the polymer-coated quantum dots, we have increased the stability of the nanoparticles while maintaining a small hydrodynamic size. Finally, we have investigated the use of the low-binding, hydroxyl quantum dots in tissue staining applications, where nonspecific binding presents a considerable challenge to detection sensitivity and specificity. A number of biomolecule conjugation techniques were examined for the coupling of quantum dots to antibody targeting molecules and preliminary staining experiments were performed. en_US
dc.description.degree Ph.D. en_US
dc.identifier.uri http://hdl.handle.net/1853/31845
dc.publisher Georgia Institute of Technology en_US
dc.subject Nanoparticles en_US
dc.subject Nanotechnology en_US
dc.subject Quantum dots en_US
dc.subject Gold nanoparticles en_US
dc.subject Polymer coatings en_US
dc.subject Diagnostics en_US
dc.subject Nonspecific binding en_US
dc.subject Immunohistochemistry en_US
dc.subject.lcsh Cancer Diagnosis
dc.subject.lcsh Semiconductors
dc.subject.lcsh Semiconductor nanoparticles
dc.subject.lcsh Surface chemistry
dc.title Development of polymer-coated nanoparticle imaging agents for diagnostic applications en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Nie, Shuming
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 422e2692-c56b-49f5-8899-cc305444af91
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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