UC San Diego

Lanthanides are a powerful yet versatile family of elements that are pivotal players in an array of industries ranging from lasers, lighting, magnets to photovoltaics. The prevalence of lanthanides is due to highly desirable properties including the unique ability to upconvert lower energy light into higher energy emissions; long luminescent lifetimes; minimal autofluorescence; no photobleaching and photoblinking; and the highest number of unpaired electrons which result in record-high relaxivities. However, despite their great potential, the overall translatability of lanthanides for biomedical imaging modalities such as photoluminescence imaging (PL) and magnetic resonance imaging (MRI) has greatly suffered from inefficiencies in terms of light absorption and specificity of signal.

This dissertation is dedicated to optimizing the design of colloidal lanthanide nanoparticles (NPs) as contrast agents to increase the overall detection sensitivity and target specificity. Sensitivity and specificity can be increased in one of two ways: (1) increase the signal; (2) decrease the background. The first theme explores the crucial role of strain engineering in the design of heavily doped core-shell (CS) upconverting NPs. We achieve an increase in the signal by expanding excitation to a more biological friendly wavelength and increasing sensitizer concentrations while maintaining uniform, concentric, coherent heteroepitaxial core-shells. The second theme investigates the potential of harnessing the high relaxivities of ultrasmall gadolinium NPs for spatiotemporal control of MRI contrast. Within this theme, we explore an alternative strategy to decrease the background by effective switching “OFF” MRI contrast enhancement which is otherwise always “ON.”

Chapter of introduction commences this journey with the fundamental physics and chemistry of lanthanides, discusses the unique features of colloidal lanthanide NPs, provides an overview of the various imaging modalities for biomedical imaging, summarizes the state-of-the-art in lanthanide NP contrast agents, highlights the major challenges in the bioimaging field, and justifies the theme for this doctoral dissertation.

Chapter 1 explores the role of strain engineering in the synthesis of heavily doped CS lanthanide-doped NPs. We show a tensile host lattice containing high levels of Neodymium to the conventional upconverting core enables shifting excitation to a biobenign wavelength, therefore, increasing the overall signal.

Chapter 2 develops a pH-activatable probe capable of spatiotemporal control of contrast for MRI to decrease background. We show the encapsulation of Gadolinium NPs within a bioresponsive polymer matrix as an efficient method of creating an “ON/OFF” signal. We introduce a simple yet elegant ligand-less method of targeting for MRI contrast agents.

Chapter 3 analyzes the current trends in the field and provides an outlook on the future of lanthanides for bioimaging applications.